Scholars@Duke
Chin-Ho Chen

Chin-Ho Chen

Professor Emeritus in Surgery
Surgery, Surgical Sciences

Scholarly Works

Discovery of 4-Quinazolinone-Containing Phenylalanine Derivatives as Potent, Resistant-Tolerant HIV Capsid Inhibitors.

Journal article MedComm (2020) · May 2026 The HIV-1 capsid (CA) is a validated antiviral target that plays critical roles in both the early and late stages of the viral life cycle. Using structure-based strategy, we designed and synthesized a series of phenylalanine derivatives containing a 4-quin ... Full text Link to item Cite

Discovery of novel diarylpyrimidine derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors: Design, synthesis and biological activity evaluation.

Journal article Bioorg Chem · March 2026 Our previous efforts have led to the development of potent NNRTI K-5a2, but it suffered from poor metabolic stability and aqueous solubility. Another work resulted in compounds XJ2-56 and XJ2-90 with reduced activity against the Y188L mutant strain. In thi ... Full text Link to item Cite

Hexakisphosphate (IP6) potentiates HIV-1 maturation inhibitor binding at the CA-SP1 junction: insights from molecular modeling and biophysical assays.

Journal article Int J Biol Macromol · November 2025 Bevirimat (BVM) and related compounds act as HIV maturation inhibitors (MIs), impeding protease-mediated cleavage of the Gag polyprotein by binding to and stabilizing the capsid (CA) and spacer peptide 1 (SP1) domains (CA-SP1). The CA-SP1 six-helix bundle ... Full text Link to item Cite

Development of enhanced HIV-1 non-nucleoside reverse transcriptase inhibitors with improved resistance and pharmacokinetic profiles.

Journal article Sci Adv · May 30, 2025 HIV-1 infection is a manageable chronic condition, with non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs) remaining a cornerstone of antiretroviral therapy. Nevertheless, drug resistance to existing therapeutics is a serious and immediate conc ... Full text Link to item Cite

Anti-HIV diterpenoids from Daphne pseudomezereum.

Journal article Phytochemistry · April 2025 The plants of the genus Daphne (Thymelaeaceae) are known to be sources of anti-HIV diterpenoids. Therefore, the present study focused on investigating the anti-HIV diterpenoids in Daphne pseudomezereum, for which the isolation of diterpenoids has not been ... Full text Link to item Cite

Identification of anti-HIV cycloartane triterpenoids from Actaea vaginata using UPLC‐QTOF‐MS/MS, DFT calculations, docking, and molecular dynamics studies

Journal article Journal of Molecular Structure · February 15, 2025 Structurally diverse triterpenoids have shown potential as pharmaceutical precursors for HIV treatment. Our previous research led to the discovery of a potent antiviral cycloartane triterpenoid derivative, (20S,24S)-15β,16β-diacetoxy-18,24;20,24-diepoxy-9, ... Full text Cite

Recent progress on triterpenoid derivatives and their anticancer potential.

Journal article Phytochemistry · January 2025 Cancer poses a significant global public health challenge, with commonly used adjuvant or neoadjuvant chemotherapy often leading to adverse side effects and drug resistance. Therefore, advancing cancer treatment necessitates the ongoing development of nove ... Full text Link to item Cite

Daphnane diterpenoid orthoesters with an odd-numbered aliphatic side chain from Daphne pedunculata.

Journal article J Nat Med · September 2024 Daphnane diterpenoids were recognized for their extensive range of potent biological activities. In the present study, phytochemical investigation including LC-MS/MS analysis resulted in the identification of five daphnane diterpenoid orthoesters (1-5). Am ... Full text Link to item Cite

Structure-based design, synthesis, and biological characterization of indolylarylsulfone derivatives as novel human immunodeficiency virus type 1 inhibitors with potent antiviral activities and favorable drug-like profiles.

Journal article J Med Virol · August 2024 In the current antiretroviral landscape, continuous efforts are still needed to search for novel chemotypes of human immunodeficiency virus type 1 (HIV-1) inhibitors with improved drug resistance profiles and favorable drug-like properties. Herein, we repo ... Full text Link to item Cite

Daphnepedunins G and H, anti-HIV macrocyclic 3,4-seco-daphnane orthoesters from Daphne pedunculata.

Journal article J Nat Med · January 2024 Daphnepedunins G (1) and H (2) with unusual macrocyclic 3,4-seco-daphnane orthoester structure were isolated from Daphne pedunculata. Their structures were determined by physicochemical and spectroscopic analyses combined with synthetic methods, including ... Full text Link to item Cite

LC-MS identification, isolation, and structural elucidation of anti-HIV macrocyclic daphnane orthoesters from Edgeworthia chrysantha.

Journal article Fitoterapia · January 2024 The occurrence of macrocyclic daphnane orthoesters (MDOs) with a 1-alkyl group originating from a C14 aliphatic chain is extremely limited in the plant kingdom and has only been isolated from Edgeworthia chrysantha. In the present study, LC-ESI-MS/MS analy ... Full text Link to item Cite

Discovery of novel diarypyrimidine derivatives bearing six-membered non-aromatic heterocycles as potent HIV-1 NNRTIs with improved anti-resistance and drug-like profiles.

Journal article Eur J Med Chem · October 5, 2023 Taking our previously reported HIV-1 NNRTIs BH-11c and XJ-10c as lead compounds, series of novel diarypyrimidine derivatives bearing six-membered non-aromatic heterocycles were designed to improve anti-resistance and drug-like profiles. According to the th ... Full text Link to item Cite

Anti-HIV Potential of Beesioside I Derivatives as Maturation Inhibitors: Synthesis, 3D-QSAR, Molecular Docking and Molecular Dynamics Simulations.

Journal article Int J Mol Sci · January 11, 2023 HIV-1 maturation is the final step in the retroviral lifecycle that is regulated by the proteolytic cleavage of the Gag precursor protein. As a first-in-class HIV-1 maturation inhibitor (MI), bevirimat blocks virion maturation by disrupting capsid-spacer p ... Full text Open Access Link to item Cite

Daphnepedunins A-F, Anti-HIV Macrocyclic Daphnane Orthoester Diterpenoids from Daphne pedunculata.

Journal article J Nat Prod · December 23, 2022 From the whole plant of Daphne pedunculata, 12 macrocyclic daphnane diterpenoids, including six new compounds, daphnepedunins A-F (1-4, 9, and 10), were isolated. Their structures were elucidated by physiochemical and spectroscopic data analysis, the modif ... Full text Link to item Cite

Tigliane-Type Diterpene Esters from the Fruits of Shirakiopsis indica and Their Anti-HIV Activity.

Journal article J Nat Prod · November 25, 2022 Four new diterpene esters, shirakindicans A-D (1-4), along with eight related known diterpene esters (5-12), were isolated from the fruits of the Bangladeshi medicinal plant Shirakiopsis indica. The structures of 1-4 were elucidated by spectroscopic data a ... Full text Link to item Cite

Anti-HIV Macrocyclic Daphnane Orthoesters with an Unusual Macrocyclic Ring from Edgeworthia chrysantha.

Journal article J Nat Prod · October 28, 2022 Edgeworthianins A-E (1-5) were isolated from Edgeworthia chrysantha as a class of macrocyclic daphnane orthoesters with an unusual macrocyclic ring formed from a C14 aliphatic chain. Their structures were elucidated by extensive physicochemical and spectro ... Full text Link to item Cite

Quinolizidines as Novel SARS-CoV-2 Entry Inhibitors.

Journal article Int J Mol Sci · August 25, 2022 COVID-19, caused by the highly transmissible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has rapidly spread and become a pandemic since its outbreak in 2019. We have previously discovered that aloperine is a new privileged scaffold that c ... Full text Link to item Cite

Anti-HIV Tigliane-Type Diterpenoids from the Aerial Parts of Wikstroemia lichiangensis.

Journal article J Nat Prod · June 24, 2022 Tigliane-type diterpenoids have attracted much attention in drug discovery since they have been reported to exhibit remarkable biological effects, such as tumor-promoting, antineoplastic, and anti-HIV activities. In continuing our efforts to discover novel ... Full text Link to item Cite

Iridoids and sesquiterpenoids from Valeriana jatamansi and their anti-influenza virus activities.

Journal article Bioorg Chem · April 2022 Twenty-one new iridoids, jatamansidoids A-U (1-12, 21-26, 32, 35 and 36), two new natural ones, jatamansidoids V (37) and W (38), eighteen known ones (13-20, 27-31, 33 and 34), together with three patchoulol-type sesquiterpenoids (39-41), were isolated fro ... Full text Link to item Cite

New phorbol ester derivatives as potent anti-HIV agents.

Journal article Bioorg Med Chem Lett · October 15, 2021 Tigliane esters show many biological activities, including anti-HIV-1 activity. Our aim in this study was to establish structure-anti-HIV activity relationships for four series of tigliane-type diterpenoids. We synthesized and evaluated 29 new phorbol este ... Full text Link to item Cite

Design, synthesis, and antiviral activity of phenylalanine derivatives as HIV-1 capsid inhibitors.

Journal article Bioorg Med Chem · October 15, 2021 The HIV-1 Capsid (CA) is considered as a promising target for the development of potent antiviral drugs, due to its multiple roles during the viral life cycle. Herein, we report the design, synthesis, and antiviral activity evaluation of series of novel ph ... Full text Link to item Cite

Hyperdioxanes, dibenzo-1,4-dioxane derivatives from the roots of Hypericum ascyron.

Journal article J Nat Med · September 2021 Six dibenzo-1,4-dioxane derivatives (1-6) were isolated from the roots of a Hypericaceous plant Hypericum ascyron. Spectroscopic analyses revealed 2 and 4-6 to be new compounds. The partial racemic natures of 1-3 were concluded by chiral HPLC analyses, whi ... Full text Link to item Cite

Identification of anti-HIV macrocyclic daphnane orthoesters from Wikstroemia ligustrina by LC-MS analysis and phytochemical investigation.

Journal article J Nat Med · September 2021 Macrocyclic daphnane orthoesters (MDOs) have attracted significant research interest for the drug discovery to cure HIV infection based on the "Shock and Kill" strategy. In the present study, the first chemical study on Wikstroemia ligustrina (Thymelaeacea ... Full text Link to item Cite

LC-MS Identification, Isolation, and Structural Elucidation of Anti-HIV Tigliane Diterpenoids from Wikstroemia lamatsoensis.

Journal article J Nat Prod · August 27, 2021 Structurally diverse tigliane diterpenoids have drawn significant research interest for drug discovery over many decades. Using LC-MS-guided fractionation and separation, the first phytochemical investigation on Wikstroemia lamatsoensis led to the isolatio ... Full text Link to item Cite

Design, synthesis, and structure activity relationship analysis of new betulinic acid derivatives as potent HIV inhibitors.

Journal article Eur J Med Chem · April 5, 2021 Prior modification of betulinic acid (1), a natural product lead with promising anti-HIV activity, produced 3-O-(3',3'-dimethylsuccinyl)betulinic acid (bevirimat, 3), the first-in-class HIV maturation inhibitor. After 3-resistant variants were found during ... Full text Link to item Cite

Design, synthesis, and evaluation of "dual-site"-binding diarylpyrimidines targeting both NNIBP and the NNRTI adjacent site of the HIV-1 reverse transcriptase.

Journal article Eur J Med Chem · February 5, 2021 Inspired by our previous efforts to improve the drug-resistance profiles of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs), a novel series of "dual-site" binding diarylpyrimidine (DAPY) derivatives targeting both the NNRTI adjacent site and ... Full text Link to item Cite

Design and Synthesis of Quinolizidine Derivatives as Influenza Virus and HIV-1 Inhibitors.

Journal article Curr Med Chem · 2021 BACKGROUND: We have previously reported that a quinolizidine natural product, aloperine, and its analogs can inhibit influenza virus and/or HIV-1 at low μM concentrations. OBJECTIVE: The main goal of this study was to further optimize aloperine for improve ... Full text Link to item Cite

Anti-HIV Tigliane Diterpenoids from Wikstroemia scytophylla.

Journal article J Nat Prod · December 24, 2020 During a chemical investigation of Wikstroemia scytophylla, three new [wikstrocins A-C (1-3)] and three known tigliane diterpenoids (4-6) were isolated. The structures of the new compounds were elucidated from extensive physiochemical and spectroscopic ana ... Full text Link to item Cite

Isolation, Structural Elucidation, and Anti-HIV Activity of Daphnane Diterpenoids from Daphne odora.

Journal article J Nat Prod · November 25, 2020 Five new [daphneodorins D-H (1, 5, and 10-12)] and seven known daphnane diterpenoids (2-4 and 6-9) were isolated from Daphne odora. The structures of the new compounds were elucidated by extensive physicochemical and spectroscopic analysis. The isolated co ... Full text Link to item Cite

Novel Betulinic Acid-Nucleoside Hybrids with Potent Anti-HIV Activity.

Journal article ACS Med Chem Lett · November 12, 2020 Novel betulinic/betulonic acid-nucleoside hybrids were synthesized as possible new anti-HIV agents. Among the synthesized hybrids, two compounds were highly effective against HIV. Compared with AZT and DSB, compounds 10a (IC50 = 0.0078 μM, CC50 = 9.6 μM) a ... Full text Link to item Cite

Paliasanines A-E, 3,4-Methylenedioxyquinoline Alkaloids Fused with a Phenyl-14-oxabicyclo[3.2.1]octane Unit from Melochia umbellata var. deglabrata.

Journal article J Nat Prod · October 23, 2020 Five new quinoline alkaloids, paliasanines A-E (1-5), and 17 known compounds (6-22) were isolated from a methanol extract of Melochia umbellata var. deglabrata leaves. Their chemical structures were elucidated by analysis of HRMS and 1D and 2D NMR spectros ... Full text Link to item Cite

Discovery of potential dual-target prodrugs of HIV-1 reverse transcriptase and nucleocapsid protein 7.

Journal article Bioorg Med Chem Lett · August 15, 2020 In the present work, we described the design, synthesis and biological evaluation of a novel series of potential dual-target prodrugs targeting the HIV-1 reverse transcriptase (RT) and nucleocapsid protein 7 (NCp7) simultaneously. Among them, the most effe ... Full text Link to item Cite

Bioactive ent-isopimarane diterpenoids from Euphorbia neriifolia.

Journal article Phytochemistry · July 2020 Twelve ent-isopimarane diterpenoids, including six undescribed ones, eupnerias J-O, were isolated from the stem barks of Euphorbia neriifolia L. Structurally, eupnerias J-M were the first examples of 18 (or 19)-norditerpenoid with ent-isopimarane skeleton ... Full text Link to item Cite

Anti-HIV tigliane diterpenoids from Reutealis trisperma.

Journal article Phytochemistry · June 2020 Bioassay-guided fractionation of the n-butanol extract from the branches and leaves of Reutealis trisperma resulted in the isolation of six undescribed (crotignoids L ~ Q) together with two known (12-deoxyphorbol-13-hexadecanoate and 12-deoxyphorbol-13-myr ... Full text Link to item Cite

Design, Synthesis, and Mechanism Study of Benzenesulfonamide-Containing Phenylalanine Derivatives as Novel HIV-1 Capsid Inhibitors with Improved Antiviral Activities.

Journal article J Med Chem · May 14, 2020 The HIV-1 CA protein has gained remarkable attention as a promising therapeutic target for the development of new antivirals, due to its pivotal roles in HIV-1 replication (structural and regulatory). Herein, we report the design and synthesis of three ser ... Full text Link to item Cite

Design, synthesis and structure-activity relationships of 4-phenyl-1H-1,2,3-triazole phenylalanine derivatives as novel HIV-1 capsid inhibitors with promising antiviral activities.

Journal article Eur J Med Chem · March 15, 2020 HIV-1 CA is involved in different stages of the viral replication cycle, performing essential roles in both early (uncoating, reverse transcription, nuclear import, integration) and late events (assembly). Recent efforts have demonstrated HIV-1 CA protein ... Full text Link to item Cite

Rapid Recognition and Targeted Isolation of Anti-HIV Daphnane Diterpenes from Daphne genkwa Guided by UPLC-MSn.

Journal article J Nat Prod · January 24, 2020 Daphnane diterpenes with a 5/7/6-tricyclic ring system exhibit potent anti-HIV activity but are found in low abundance as plant natural products. In this study, an effective approach based on mass spectrometric fragmentation pathways was conducted to speci ... Full text Link to item Cite

Daphneodorins A-C, Anti-HIV Gnidimacrin Related Macrocyclic Daphnane Orthoesters from Daphne odora.

Journal article Org Lett · January 3, 2020 Three novel gnidimacrin related macrocyclic daphnanes (GMDs), daphneodorins A-C (2-4), were isolated from Daphne odora Thunb., together with gnidimacrin (1). Their structures were established by extensive physicochemical and spectroscopic analyses. Compoun ... Full text Link to item Cite

Carbazole Alkaloids from Clausena anisum-olens: Isolation, Characterization, and Anti-HIV Evaluation.

Journal article Molecules · December 26, 2019 Two new carbazole alkaloids (1,2) and six known carbazole alkaloids (3-8) were isolated from Clausena anisum-olens. Their structures were elucidated based on extensive spectroscopic analysis. All isolated compounds (1-8) were evaluated for their anti-HIV e ... Full text Link to item Cite

Identification of highly potent and selective Cdc25 protein phosphatases inhibitors from miniaturization click-chemistry-based combinatorial libraries.

Journal article Eur J Med Chem · December 1, 2019 Cell division cycle 25 (Cdc25) protein phosphatases play key roles in the transition between the cell cycle phases and their association with various cancers has been widely proven, which makes them ideal targets for anti-cancer treatment. Though several C ... Full text Link to item Cite

Synthesis and Structure-Activity Relationship Correlations of Gnidimacrin Derivatives as Potent HIV-1 Inhibitors and HIV Latency Reversing Agents.

Journal article J Med Chem · August 8, 2019 Currently, due to the HIV latency mechanism, the search continues for effective drugs to combat this issue and provide a cure for AIDS. Gnidimacrin activates latent HIV-1 replication and inhibits HIV-1 infection at picomolar concentrations. This natural di ... Full text Link to item Cite

Potent Anti-HIV Ingenane Diterpenoids from Euphorbia ebracteolata.

Journal article J Nat Prod · June 28, 2019 Two new (1 and 2) and 14 known (3-16) ingenane diterpenoids were isolated from the roots of Euphorbia ebracteolata by bioassay-guided fractionation together with UPLC-MS n analysis. The absolute configurations of the new diterpenoids were established from ... Full text Link to item Cite

Design, synthesis, and biologic evaluation of novel galloyl derivatives as HIV-1 RNase H inhibitors.

Journal article Chem Biol Drug Des · April 2019 Human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated ribonuclease H (RNase H) remains as the only enzyme encoded within the viral genome not targeted by current antiviral drugs. In this work, we report the design, synthesis, and biologi ... Full text Link to item Cite

Discovery and synthesis of novel beesioside I derivatives with potent anti-HIV activity.

Journal article Eur J Med Chem · March 15, 2019 In this study, 12 known cycloartane triterpenoids (1-12) with four different skeletons isolated from the roots of Souliea vaginata were screened for the first time for in vitro anti-HIV activity using AZT as a standard. Among the compounds, beesioside I (1 ... Full text Link to item Cite

Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties.

Journal article J Med Chem · February 14, 2019 To address drug resistance to HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs), a series of novel diarylpyrimidine (DAPY) derivatives targeting "tolerant region I" and "tolerant region II" of the NNRTIs binding pocket (NNIBP) were designed ut ... Full text Link to item Cite

Discovery of novel 1,4-disubstituted 1,2,3-triazole phenylalanine derivatives as HIV-1 capsid inhibitors.

Journal article RSC Adv · 2019 The HIV-1 capsid (CA) protein plays crucial roles in both early and late stages of the viral life cycle, which has intrigued researchers to target it to develop anti-HIV drugs. Accordingly, in this research, we report the design, synthesis and biological e ... Full text Link to item Cite

Discovery of phenylalanine derivatives as potent HIV-1 capsid inhibitors from click chemistry-based compound library.

Journal article Eur J Med Chem · October 5, 2018 The HIV-1 capsid (CA) protein plays essential roles in both early and late stages of HIV-1 replication and is considered an important, clinically unexploited therapeutic target. As such, small drug-like molecules that inhibit this critical HIV-1 protein ha ... Full text Link to item Cite

Identification, structural modification, and dichotomous effects on human immunodeficiency virus type 1 (HIV-1) replication of ingenane esters from Euphorbia kansui.

Journal article Eur J Med Chem · August 5, 2018 Euphorbia kansui showed potent anti-HIV-1 activity during screening of a library composed of plant extracts from Euphorbiaceae and Thymelaeaceae families. Bioassay-guided isolation led to identification of ingenane esters as the active compounds. Further c ... Full text Link to item Cite

Kleinhospitine E and Cycloartane Triterpenoids from Kleinhovia hospita.

Journal article J Nat Prod · July 27, 2018 A novel cycloartane triterpenoid alkaloid, kleinhospitine E (1), six new cycloartane triterpenoids (2-7), three known cycloartane triterpenoids (8-10), and taraxerone (11) were isolated from a methanol extract of Kleinhovia hospita. Their structures were e ... Full text Link to item Cite

Role of Porphyromonas gingivalis outer membrane vesicles in oral mucosal transmission of HIV.

Journal article Sci Rep · June 11, 2018 The association between mucosal microbiota and HIV-1 infection has garnered great attention in the field of HIV-1 research. Previously, we reported a receptor-independent HIV-1 entry into epithelial cells mediated by a Gram-negative invasive bacterium, Por ... Full text Link to item Cite

Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus.

Journal article Eur J Med Chem · May 10, 2018 Inspired by our previous efforts on the modifications of diarylpyrimidines as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTI) and reported crystallography study, novel diarylnicotinamide derivatives were designed with a "triazole tail" occupy ... Full text Link to item Cite

Terpenes from Euphorbia antiquorum and Their in Vitro Anti-HIV Activity.

Journal article Chem Biodivers · May 2018 Three new compounds (1 - 3), including two euphane type triterpenes, 24,24-dimethoxy-25,26,27-trinoreuphan-3β-ol (1) and (24S)-24-hydroperoxyeupha-8,25-dien-3β-ol (2), and an ent-atisine diterpene, ent-atisane-3α,16α,17-triol (3), were isolated from an ace ... Full text Link to item Cite

Elimination of HIV-1 Latently Infected Cells by Gnidimacrin and a Selective HDAC Inhibitor.

Journal article ACS Med Chem Lett · March 8, 2018 We have previously reported gnidimacrin (GM), a protein kinase C (PKC) agonist, significantly reduces the frequency of HIV-1 latently infected cells in peripheral blood mononuclear cells (PBMCs) from patients undergoing successful antiretroviral therapy at ... Full text Link to item Cite

Diterpenes from the stem bark of Euphorbia neriifolia and their in vitro anti-HIV activity.

Journal article Phytochemistry · January 2018 Six previously undescribed diterpenoids, named euphorantins S-T and euphorneroids A-D, including ingol and ent-atisane types, along with eleven known diterpenoids, were isolated from Euphorbia neriifolia. Their structures were elucidated on the basis of ex ... Full text Link to item Cite

Structure Optimization of Aloperine Derivatives as HIV-1 Entry Inhibitors.

Journal article ACS Med Chem Lett · November 9, 2017 As a step toward developing novel anti-HIV agents, we have identified a class of quinolizidines, including aloperine, that inhibit HIV at 1-5 μM by blocking viral entry. In this study, we have optimized the structure of aloperine and derived compounds with ... Full text Link to item Cite

Anti-inflammatory and Anti-HIV Compounds from Swertia bimaculata.

Journal article Planta Med · November 2017 Three new compounds (1 - 3), including a sesterterpenoid, aspterpenacid C (1), with an unusual 5/3/7/6/5 pentacyclic skeleton, together with seven known ones (4 - 10), were isolated from the ethanol extract of the traditional Chinese medicinal plant Swerti ... Full text Link to item Cite

Drug-like property-driven optimization of 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors against rilpivirine-resistant mutant virus.

Journal article Bioorg Med Chem Lett · June 15, 2017 On the basis of our prior structure-activity relationship (SAR) results, our current lead optimization of 1,5-diarylanilines (DAANs) focused on the 4-substituent (R1) on the central phenyl ring as a modifiable position related simultaneously to improved dr ... Full text Link to item Cite

Incorporation of Privileged Structures into Bevirimat Can Improve Activity against Wild-Type and Bevirimat-Resistant HIV-1.

Journal article J Med Chem · October 13, 2016 Two "privileged fragments", caffeic acid and piperazine, were integrated into bevirimat producing new derivatives with improved activity against HIV-1/NL4-3 and NL4-3/V370A carrying the most prevalent bevirimat-resistant polymorphism. The activity of one o ... Full text Link to item Cite

Two new ursane-type triterpenoid saponins from Elsholtzia bodinieri.

Journal article Arch Pharm Res · June 2016 Two new ursane-type triterpenoid saponins, bodiniosides M (1) and N (2), along with three known saponins, oblonganosides I (3), pseudobuxussaponin B (4) and bodinioside A (5), were isolated from the aerial parts of Elsholtzia bodinieri. The structures of c ... Full text Link to item Cite

Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus.

Journal article J Med Chem · April 28, 2016 Three series (6, 13, and 14) of new diarylaniline (DAAN) analogues were designed, synthesized, and evaluated for anti-HIV potency, especially against the E138K viral strain with a major mutation conferring resistance to the new-generation non-nucleoside re ... Full text Link to item Cite

Carolignans from the Aerial Parts of Euphorbia sikkimensis and Their Anti-HIV Activity.

Journal article J Nat Prod · March 25, 2016 Seven new carolignans, including two pairs of enantiomers (±)-erythro-7'-methylcarolignan E (1a/1b) and (±)-threo-7'-methylcarolignan E (2a/2b), (+)-threo-carolignan E (3a), (+)-erythro-carolignan E (4a), and (-)-erythro-carolignan Z (5), together with fou ... Full text Link to item Cite

Aloperine and Its Derivatives as a New Class of HIV-1 Entry Inhibitors.

Journal article ACS Med Chem Lett · March 10, 2016 A quinolizidine-type alkaloid aloperine was found to inhibit HIV-1 infection by blocking HIV-1 entry. Aloperine inhibited HIV-1 envelope-mediated cell-cell fusion at low micromolar concentrations. To further improve the antiviral potency, more than 30 alop ... Full text Link to item Cite

Fluorinated betulinic acid derivatives and evaluation of their anti-HIV activity.

Journal article Bioorg Med Chem Lett · January 1, 2016 Several fluorinated derivatives of the anti-HIV maturation agent bevirimat (1) were synthesized and evaluated for anti-HIV replication activity. The modified positions were the C-2, C-3, C-28, and C-30 positions, either directly on the betulinic acid (2) s ... Full text Link to item Cite

Two Small Molecules Block Oral Epithelial Cell Invasion by Porphyromons gingivalis.

Journal article PLoS One · 2016 Porphyromonas gingivalis is a keystone pathogen of periodontitis. One of its bacterial characteristics is the ability to invade various host cells, including nonphagocytic epithelial cells and fibroblasts, which is known to facilitate P. gingivalis adaptat ... Full text Link to item Cite

Gnidimacrin, a Potent Anti-HIV Diterpene, Can Eliminate Latent HIV-1 Ex Vivo by Activation of Protein Kinase C β.

Journal article J Med Chem · November 12, 2015 HIV-1-latency-reversing agents, such as histone deacetylase inhibitors (HDACIs), were ineffective in reducing latent HIV-1 reservoirs ex vivo using CD4 cells from patients as a model. This deficiency poses a challenge to current pharmacological approaches ... Full text Link to item Cite

Flavonoids isolated from heat-processed Epimedium koreanum and their anti-HIV-1 activities

Journal article Helvetica Chimica Acta · August 1, 2015 Systematic phytochemical investigation on heat-processed Epimedium koreanum led to the isolation of 13 flavonoids, including five new prenyl-flavonol glycosides, koreanosides A-E (1-5, resp.). Their structures were elucidated on the basis of detailed analy ... Full text Cite

Discovery of novel non-covalent inhibitors selective to the β5-subunit of the human 20S proteasome.

Journal article Eur J Med Chem · June 15, 2015 A series of linear peptides (6a-6o) were designed based on the known non-covalent 20S proteasome inhibitors TMC-95A and compound 5 via a fragment-based approach. These compounds were synthesized and evaluated against the chymotrypsin-like activity of the h ... Full text Link to item Cite

Phenolic diterpenoid derivatives as anti-influenza a virus agents.

Journal article ACS Med Chem Lett · March 12, 2015 A series of diterpenoid derivatives based on podocarpic acid were synthesized and evaluated as anti-influenza A virus agents. Several of the novel podocarpic acid derivatives exhibited nanomolar activities against an H1N1 influenza A virus (A/Puerto Rico/8 ... Full text Link to item Cite

Discovery of novel 5-fluoro-N2,N4-diphenylpyrimidine-2,4-diamines as potent inhibitors against CDK2 and CDK9.

Journal article Medchemcomm · March 1, 2015 Based on a 3D-QSAR pharmacophore derived from a diverse set of known cyclin-dependent kinase 9 (CDK9) inhibitors and a composite pharmacophore extracted from the complex structure of flavopiridol (FVP)-CDK9, thirty novel 5-fluoro-N2,N4-diphenylpyrimidine-2 ... Full text Link to item Cite

Fimbriae-mediated outer membrane vesicle production and invasion of Porphyromonas gingivalis.

Journal article Microbiologyopen · February 2015 Porphyromonas gingivalis is a keystone periopathogen that plays an essential role in the progress of periodontitis. Like other gram-negative bacteria, the ability of P. gingivalis to produce outer membrane vesicles is a strategy used to interact with, and ... Full text Link to item Cite

Functional Advantages of Porphyromonas gingivalis Vesicles.

Journal article PLoS One · 2015 Porphyromonas gingivalis is a keystone pathogen of periodontitis. Outer membrane vesicles (OMVs) have been considered as both offense and defense components of this bacterium. Previous studies indicated that like their originating cells, P. gingivalis vesi ... Full text Link to item Cite

Inhibitory effect of b-AP15 on the 20S proteasome.

Journal article Biomolecules · October 14, 2014 The 26S proteasome is a cellular proteolytic complex containing 19S regulatory particles and the 20S core proteasome. It was reported that the small molecule b-AP15 targets the proteasome by inhibiting deubiquitination of the 19S regulatory particles of th ... Full text Link to item Cite

Identification and synthesis of quinolizidines with anti-influenza a virus activity.

Journal article ACS Med Chem Lett · August 14, 2014 Influenza A virus infection causes a contagious respiratory illness that poses a threat to human health. However, there are limited anti-influenza A therapeutics available, which is further compounded by the emergence of drug resistant viruses. In this stu ... Full text Link to item Cite

Porphyromonas gingivalis-mediated Epithelial Cell Entry of HIV-1.

Journal article J Dent Res · August 2014 HIV-1 relies on the host's cell machinery to establish a successful infection. Surface receptors, such as CD4, CCR5, and CXCR4 of T cells and macrophages, are essential for membrane fusion of HIV-1, an initiate step in viral entry. However, it is not well ... Full text Link to item Cite

Optimization of the antiviral potency and lipophilicity of halogenated 2,6-diarylpyridinamines as a novel class of HIV-1 NNRTIS.

Journal article ChemMedChem · July 2014 Nineteen new halogenated diarylpyridinamine (DAPA) analogues modified at the phenoxy C-ring were synthesized and evaluated for anti-HIV activity and certain drug-like properties. Ten compounds showed high anti-HIV activity (EC50 <10 nM). In particular, (E) ... Full text Link to item Cite

Isolation, structure determination, and anti-HIV evaluation of tigliane-type diterpenes and biflavonoid from Stellera chamaejasme.

Journal article J Nat Prod · May 24, 2013 Five novel tigliane-type diterpenes, stelleracins A-E (3-7), a novel flavanone dimer, chamaeflavone A (8), and six known compounds were isolated from the roots of Stellera chamaejasme. Their structures were elucidated by extensive spectroscopic analyses. T ... Full text Link to item Cite

In-depth analysis of the interaction of HIV-1 with cellular microRNA biogenesis and effector mechanisms.

Journal article mBio · April 16, 2013 UNLABELLED: The question of how HIV-1 interfaces with cellular microRNA (miRNA) biogenesis and effector mechanisms has been highly controversial. Here, we first used deep sequencing of small RNAs present in two different infected cell lines (TZM-bl and C81 ... Full text Link to item Cite

New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1.

Journal article J Med Chem · March 14, 2013 Bevirimat (1, BVM) is an anti-HIV agent that blocks HIV-1 replication by interfering with HIV-1 Gag-SP1 processing at a late stage of viral maturation. However, clinical trials of 1 have revealed a high baseline drug resistance that is attributed to natura ... Full text Link to item Cite

Synthesis and biological evaluation of novel spin labeled 18β-glycyrrhetinic acid derivatives.

Journal article Bioorg Med Chem Lett · December 15, 2012 Eighteen novel spin-labeled 18β-glycyrrhetinic acid (GA) derivatives were designed, synthesized, and evaluated for cytotoxicity against four human tumor cell lines (A-549, DU-145, KB and KBvin). Most of the derivatives showed more significant cytotoxicity ... Full text Link to item Cite

Anti-AIDS agents 90. novel C-28 modified bevirimat analogues as potent HIV maturation inhibitors.

Journal article J Med Chem · September 27, 2012 In a continuing study of bevirimat (2), the anti-HIV-maturation clinical trials agent, 28 new betulinic acid (BA, 1) derivatives were designed and synthesized. Among these compounds, 17, with a C-28 MEM ester moiety, and 22, with a C-28 ethyl hexanoate, in ... Full text Link to item Cite

Design, synthesis, and preclinical evaluations of novel 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) drug candidates.

Journal article J Med Chem · August 23, 2012 Twenty-one new 4-substituted diarylaniline compounds (DAANs) (series 13, 14, and 15) were designed, synthesized, and evaluated against wild-type and drug resistant HIV-1 viral strains. As a result, approximately a dozen new DAANs showed high potency with l ... Full text Link to item Cite

Synthesis of betulinic acid derivatives as entry inhibitors against HIV-1 and bevirimat-resistant HIV-1 variants.

Journal article Bioorg Med Chem Lett · August 15, 2012 Betulinic acid derivatives modified at the C28 position are HIV-1entry inhibitors such as compound A43D; however, modified at the C3 position instead of C28 give HIV-1 maturation inhibitor such as bevirimat. Bevirimat exhibited promising pharmacokinetic pr ... Full text Link to item Cite

Blocking HIV-1 entry by a gp120 surface binding inhibitor.

Journal article Bioorg Med Chem Lett · May 1, 2012 We report the mode of action of a proteomimetic compound that binds to the exterior surface of gp120 and blocks HIV-1 entry into cells. Using a one cycle time-of-addition study and antibody competition binding studies, we have determined that the compound ... Full text Link to item Cite

Design and synthesis of naphthoquinone derivatives as antiproliferative agents and 20S proteasome inhibitors.

Journal article Bioorg Med Chem Lett · April 15, 2012 Fourteen naphthoquinone derivatives (1-14) were designed based on a putative proteasome inhibitor PI-083. These compounds were synthesized and evaluated against A549, DU145, KB, and KBvin tumor cell lines. Six compounds (2, 4, 8, 9, 10, and 13) showed anti ... Full text Link to item Cite

Anti-AIDS agents 88. Anti-HIV conjugates of betulin and betulinic acid with AZT prepared via click chemistry.

Journal article Tetrahedron Lett · April 11, 2012 In the present study, a new strategy to link AZT with betulin/betulinic acid (BA) by click chemistry was designed and achieved. This conjugation via a triazole linkage offers a new direction for modification of anti-HIV triterpenes. Click chemistry provide ... Full text Link to item Cite

Optimization of 2,4-diarylanilines as non-nucleoside HIV-1 reverse transcriptase inhibitors.

Journal article Bioorg Med Chem Lett · April 1, 2012 The current optimization of 2,4-diarylaniline analogs (DAANs) on the central phenyl ring provided a series of new active DAAN derivatives 9a-9e, indicating an accessible modification approach that could improve anti-HIV potency against wild-type and resist ... Full text Link to item Cite

Synthesis of Lithocholic Acid Derivatives as Proteasome Regulators.

Journal article ACS Med Chem Lett · 2012 Accumulation of aberrant protein aggregates, such as amyloid beta peptide (Aβ), due to decreased proteasome activities might contribute to the neurodegeneration in Alzheimer's disease. In this study, lithocholic acid derivatives 3α-O-pimeloyl-lithocholic a ... Full text Link to item Cite

Anti-AIDS agents 85. Design, synthesis, and evaluation of 1R,2R-dicamphanoyl-3,3-dimethyldihydropyrano-[2,3-c]xanthen-7(1H)-one (DCX) derivatives as novel anti-HIV agents.

Journal article Eur J Med Chem · January 2012 In this study, 1R,2R-dicamphanoyl-3,3-dimethydihydropyrano[2,3-c]xanthen-7(1H)-one (DCX) derivatives were designed and synthesized as novel anti-HIV agents against both wild-type and non-nucleoside reverse transcriptase (RT) inhibitor-resistant HIV-1 (RTMD ... Full text Link to item Cite

Oxathiazole-2-one derivative of bortezomib: Synthesis, stability and proteasome inhibition activity

Journal article Medchemcomm · November 1, 2011 Oxathiazole-2-one is a new candidate for proteasome inhibition which has not been widely explored. We describe herein the synthesis and characterization of a new oxathiazole-2-one derived from the dipeptide backbone of Bortezomib. We found that this new ox ... Full text Cite

Anti-AIDS agents 86. Synthesis and anti-HIV evaluation of 2',3'-seco-3'-nor DCP and DCK analogues.

Journal article Eur J Med Chem · October 2011 In a continuing study of novel anti-HIV agents with drug-like structures and properties, 30 1'-O-, 1'-S-, 4'-O- and 4'-substituted-2',3'-seco-3'-nor DCP and DCK analogues (8-37) were designed and synthesized. All newly synthesized seco-compounds were scree ... Full text Link to item Cite

Anti-AIDS agents 87. New bio-isosteric dicamphanoyl-dihydropyranochromone (DCP) and dicamphanoyl-khellactone (DCK) analogues with potent anti-HIV activity.

Journal article Bioorg Med Chem Lett · October 1, 2011 Six 3'R,4'R-di-O-(S)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) and two 3'R,4'R-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives were designed, synthesized, and evaluated for inhibition of HIV-1(NL4-3) replication in TZM-bl cells. ... Full text Link to item Cite

New betulinic acid derivatives as potent proteasome inhibitors.

Journal article Bioorg Med Chem Lett · October 1, 2011 In this study, 22 new betulinic acid (BA) derivatives were synthesized and tested for their inhibition of the chymotrypsin-like activity of 20S proteasome. From the SAR study, we concluded that the C-3 and C-30 positions are the pharmacophores for increasi ... Full text Link to item Cite

Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents.

Journal article Eur J Med Chem · September 2011 We prepared 1-(4'-azido-2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)cytosine (10) and its hydrochloride salt (11) as potential antiviral agents based on the favorable antiviral profiles of 4'-substituted nucleosides. Compounds 10 and 11 were synthesized from 1 ... Full text Link to item Cite

The role of dynamin in HIV type 1 Env-mediated cell-cell fusion.

Journal article AIDS Res Hum Retroviruses · September 2011 HIV-1 envelope glycoproteins are the key viral proteins that mediate HIV-1 entry and cell-cell fusion. In contrast to HIV-1 entry, the mechanism of HIV-1 Env-mediated cell-cell fusion is relatively unclear. This study demonstrated that dynasore, a dynamin ... Full text Link to item Cite

Stelleralides A-C, novel potent anti-HIV daphnane-type diterpenoids from Stellera chamaejasme L.

Journal article Org Lett · June 3, 2011 Three novel 1-alkyldaphnane-type diterpenes, stelleralides A-C (4-6), and five known compounds were isolated from the roots of Stellera chamaejasme L. The structures of 4-6 were elucidated by extensive spectroscopic analyses. Several isolated compounds sho ... Full text Link to item Cite

[Design, synthesis and evaluation of novel 2H-1, 4-benzodiazepine-2-ones as inhibitors of HIV-1 transcription].

Journal article Yao Xue Xue Bao · June 2011 HIV-1 trans-activator of transcription (Tat) plays a critical role in HIV-1 transcription. Based on the beta-turn motif present in HIV-1 Tat, a series of novel benzodiazepine analogs were designed as beta-turn mimetics and prepared from p-chloro-nitrobenze ... Link to item Cite

Synthesis and proteasome inhibition of lithocholic acid derivatives.

Journal article Bioorg Med Chem Lett · April 1, 2011 A new class of proteasome inhibitors was synthesized using lithocholic acid as a scaffold. Modification at the C-3 position of lithocholic acid with a series of acid acyl groups yielded compounds with a range of potency on proteasome inhibition. Among them ... Full text Link to item Cite

Picomolar dichotomous activity of gnidimacrin against HIV-1.

Journal article PLoS One · 2011 Highly active antiretroviral therapy (HAART) has offered a promising approach for controlling HIV-1 replication in infected individuals. However, with HARRT, HIV-1 is suppressed rather than eradicated due to persistence of HIV-1 in latent viral reservoirs. ... Full text Link to item Cite

Design, synthesis, and evaluation of diarylpyridines and diarylanilines as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.

Journal article J Med Chem · December 9, 2010 On the basis of the structures and activities of our previously identified non-nucleoside reverse transcriptase inhibitors (NNRTIs), we designed and synthesized two sets of derivatives, diarylpyridines (A) and diarylanilines (B), and tested their anti-HIV- ... Full text Open Access Link to item Cite

Anti-AIDS agents 79. Design, synthesis, molecular modeling and structure-activity relationships of novel dicamphanoyl-2',2'-dimethyldihydropyranochromone (DCP) analogs as potent anti-HIV agents.

Journal article Bioorg Med Chem · September 15, 2010 In a continued study, 23 3'R,4'R-di-O-(-)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) derivatives (5-27) were synthesized, and screened for anti-HIV activity against both a non-drug-resistant NL4-3 strain and multiple reverse transcriptase ... Full text Link to item Cite

Conjugates of betulin derivatives with AZT as potent anti-HIV agents.

Journal article Bioorg Med Chem · September 1, 2010 Fourteen novel conjugates of 3,28-di-O-acylbetulins with AZT were prepared as anti-HIV agents, based on our previously reported potent anti-HIV triterpene leads, including 3-O-acyl and 3,28-di-O-acylbetulins. Nine of the conjugates (49-53, 55, 56, 59, and ... Full text Link to item Cite

Synthesis and anti-HIV activity of 2'-deoxy-2'-fluoro-4'-C-ethynyl nucleoside analogs.

Journal article Bioorg Med Chem Lett · July 15, 2010 Based on the favorable antiviral profiles of 4'-substituted nucleosides, novel 1-(2'-deoxy-2'-fluoro-4'-C-ethynyl-beta-D-arabinofuranosyl)-uracil (1a), -thymine (1b), and -cytosine (2) analogs were synthesized. Compounds 1b and 2 exhibited potent anti-HIV- ... Full text Link to item Cite

Diarylaniline derivatives as a distinct class of HIV-1 non-nucleoside reverse transcriptase inhibitors.

Journal article J Med Chem · July 8, 2010 By using structure-based drug design and isosteric replacement, diarylaniline and 1,5-diarylbenzene-1,2-diamine derivatives were synthesized and evaluated against wild type HIV-1 and drug-resistant viral strains, resulting in the discovery of diarylaniline ... Full text Open Access Link to item Cite

Anti-AIDS agents 82: synthesis of seco-(3'R,4'R)-3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives as novel anti-HIV agents.

Journal article Bioorg Med Chem · June 15, 2010 Thirteen novel seco-DCK analogs (4-16) with several new skeletons were designed, synthesized and screened for in vitro anti-HIV-1 activity. Among them, three compounds (5, 13, and 16) showed moderate activity, and compound 9 exhibited the best activity wit ... Full text Link to item Cite

Anti-AIDS agents 81. Design, synthesis, and structure-activity relationship study of betulinic acid and moronic acid derivatives as potent HIV maturation inhibitors.

Journal article J Med Chem · April 22, 2010 In our continuing study of triterpene derivatives as potent anti-HIV agents, different C-3 conformationally restricted betulinic acid (BA, 1) derivatives were designed and synthesized in order to explore the conformational space of the C-3 pharmacophore. 3 ... Full text Open Access Link to item Cite

HIV entry inhibitors: progress in development and application.

Journal article Yao Xue Xue Bao · February 2010 This review discusses recent progress in the development of anti-HIV agents, with emphasis on small molecule HIV-1 entry inhibitors. The entry inhibitors primarily target HIV-1 envelope glycoproteins or the cellular receptors, CD4 and chemokine receptors. ... Link to item Cite

Betulinic acid derivatives as human immunodeficiency virus type 2 (HIV-2) inhibitors.

Journal article J Med Chem · December 10, 2009 We previously reported that [[N-[3beta-hydroxyllup-20(29)-en-28-oyl]-7-aminoheptyl]carbamoyl]methane (A43D, 4) was a potent HIV-1 entry inhibitor. However, 4 was inactive against HIV-2 virus, suggesting the structural requirements for targeting these two r ... Full text Link to item Cite

HIV-1 maturation inhibitors: An update

Journal article Drugs of the Future · October 1, 2009 HIV-1 maturation inhibitors are compounds other than HIV-1 protease inhibitors that inhibit HIV-1 maturation. This review focuses on triterpene derivatives, as their preclinical and clinical pharmacological profiles have been relatively well studied. Among ... Full text Cite

Discovery of diarylpyridine derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.

Journal article Bioorg Med Chem Lett · September 15, 2009 Two series (4 and 5) of diarylpyridine derivatives were designed, synthesized, and evaluated for anti-HIV-1 activity. The most promising compound, 5e, inhibited HIV-1 IIIB, NL4-3, and RTMDR1 with low nanomolar EC50 values and selectivity indexes of >10,000 ... Full text Link to item Cite

Structure-activity relationship study of novel betulinic acid analogs as potent HIV maturation inhibitors

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 16, 2009 Link to item Cite

Anti-AIDS agents. 78. Design, synthesis, metabolic stability assessment, and antiviral evaluation of novel betulinic acid derivatives as potent anti-human immunodeficiency virus (HIV) agents.

Journal article J Med Chem · May 28, 2009 In a continuing study of potent anti-HIV agents, seventeen 28,30-disubstituted betulinic acid (BA, 1) derivatives and seven novel 3,28-disubstituted BA analogues were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, compoun ... Full text Link to item Cite

HIV-1 maturation inhibitors: An update

Journal article Drugs of the Future · January 1, 2009 HIV-1 maturation inhibitors are compounds other than HIV-1 protease inhibitors that inhibit HIV-1 maturation. This review focuses on triterpene derivatives, as their preclinical and clinical pharmacological profiles have been relatively well studied. Among ... Full text Cite

Proteasome regulators: activators and inhibitors.

Journal article Curr Med Chem · 2009 This mini review covers the drug discovery aspect of both proteasome activators and inhibitors. The proteasome is involved in many essential cellular functions, such as regulation of cell cycle, cell differentiation, signal transduction pathways, antigen p ... Full text Link to item Cite

Synthesis and proteasome inhibition of glycyrrhetinic acid derivatives.

Journal article Bioorg Med Chem · July 15, 2008 This study discovered that glycyrrhetinic acid inhibited the human 20S proteasome at 22.3microM. Esterification of the C-3 hydroxyl group on glycyrrhetinic acid with various carboxylic acid reagents yielded a series of analogs with marked improved potency. ... Full text Link to item Cite

Betulinic acid derivatives that target gp120 and inhibit multiple genetic subtypes of human immunodeficiency virus type 1.

Journal article Antimicrob Agents Chemother · January 2008 Betulinic acid (BA) derivatives can inhibit human immunodeficiency virus type 1 (HIV-1) entry or maturation depending on side chain modifications. While BA derivatives with antimaturation activity have attracted considerable interest, the anti-HIV-1 profil ... Full text Link to item Cite

Synthesis and anti-HIV activity of Bif-functional triterpene derivatives

Journal article Letters in Drug Design and Discovery · October 1, 2007 We previously reported a bi-functional betulinic acid derivative, A12-2 (4), containing an optimized C-28 side chain that exhibits potent anti-HIV activity by inhibiting both HIV-1 entry and maturation. Compound 4 contains C-3 and C-28 side chains that are ... Full text Cite

Induction of a nonproductive conformational change in gp120 by a small molecule HIV type 1 entry inhibitor.

Journal article AIDS Res Hum Retroviruses · January 2007 Conformational changes in HIV-1 envelope glycoproteins, gp120 and gp41, is a dynamic process essential for HIV-1 entry. Here we show that a small molecule HIV-1 entry inhibitor, IC9564, induces a conformational change in gp120. The conformational change in ... Full text Link to item Cite

Human immunodeficiency virus type 1 resistance to the small molecule maturation inhibitor 3-O-(3',3'-dimethylsuccinyl)-betulinic acid is conferred by a variety of single amino acid substitutions at the CA-SP1 cleavage site in Gag.

Journal article J Virol · December 2006 The compound 3-O-(3',3'-dimethylsuccinyl)-betulinic acid (DSB) potently and specifically inhibits human immunodeficiency virus type 1 (HIV-1) replication by delaying the cleavage of the CA-SP1 junction in Gag, leading to impaired maturation of the viral co ... Full text Link to item Cite

Anti-AIDS agents 69. Moronic acid and other triterpene derivatives as novel potent anti-HIV agents.

Journal article J Med Chem · September 7, 2006 In a continuing structure-activity relationship study of potent anti-HIV agents, seven new triterpene derivatives were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, moronic acid derivatives 19, 20, and 21 showed signific ... Full text Link to item Cite

Inhibition of human immunodeficiency virus type 1 entry by a binding domain of Porphyromonas gingivalis gingipain.

Journal article Antimicrob Agents Chemother · September 2006 Human immunodeficiency virus (HIV) transmission through saliva is extremely low. Several oral components, including secretory immunoglobulin A and secretory leukocyte protease inhibitor, are known as potential inhibitory agents of HIV oral transmission. He ... Full text Link to item Cite

Synthesis and anti-HIV activity of bi-functional betulinic acid derivatives.

Journal article Bioorg Med Chem · April 1, 2006 Betulinic acid (BA) derivatives with a side chain at C-3 can inhibit HIV-1 maturation. On the other hand, BA derivatives with a side chain at C-28 can block HIV-1 entry. In order to combine the anti-maturation and anti-entry activities in a single molecule ... Full text Link to item Cite

Moronic acid derivatives as novel potent anti-HIV agents

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · March 26, 2006 Link to item Cite

Inhibition of HIV-1 maturation via drug association with the viral Gag protein in immature HIV-1 particles.

Journal article J Biol Chem · December 23, 2005 The small molecule 3-O-(3',3'-dimethylsuccinyl)-betulinic acid (DSB) potently inhibits human immunodeficiency virus, type 1 (HIV-1) replication by interfering with proteolytic cleavage of the viral Gag protein at a specific site. Here we have demonstrated ... Full text Link to item Cite

The discovery of a class of novel HIV-1 maturation inhibitors and their potential in the therapy of HIV.

Journal article Expert Opin Investig Drugs · June 2005 Although HIV infection is now primarily treated with reverse transcriptase and protease inhibitors, HIV therapy must look toward new drugs with novel mechanism(s) of action to both improve efficacy and address the growing problem of drug resistance. Using ... Full text Link to item Cite

Mechanism of action and resistant profile of anti-HIV-1 coumarin derivatives.

Journal article Virology · February 20, 2005 Dicamphanoyl khellactone (DCK) is a coumarin derivative that can potently inhibit HIV-1 replication. DCK does not inhibit RNA-dependent DNA synthesis. However, an HIV reverse transcriptase (RT) inhibitor-resistant strain, HIV-1/RTMDR1, is resistant to DCK. ... Full text Link to item Cite

The molecular targets of anti-HIV-1 triterpenes, an update

Journal article Medicinal Chemistry Reviews Online · January 1, 2005 Pentacyclic triterpenes have been found in many plants and can be isolated from any parts of the plant. Triterpene derivatives were shown to have biological activities including anti-HIV-1 and anti-cancer. The modes of action of the anti-HIV-1 triterpenes ... Full text Cite

Betulinic acid derivatives as HIV-1 antivirals.

Journal article Trends Mol Med · January 2005 Betulinic acid (BA) derivatives are low molecular weight organic compounds synthesized from a plant-derived natural product. Several BA derivatives are potent and highly selective inhibitors of HIV-1. Depending on the specific side-chain modification, thes ... Full text Link to item Cite

Anti-AIDS agents. 60. Substituted 3'R,4'R-di-O-(-)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) analogues as potent anti-HIV agents.

Journal article J Med Chem · July 29, 2004 Synthesis of positional isomers is a commonly used technique in drug design. Accordingly, based on prior SAR studies of 3'R,4'R-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK, 1) analogues, a series of mono- and disubstituted chromone derivatives of 3'R,4'R- ... Full text Link to item Cite

Conformation of gp120 determines the sensitivity of HIV-1 DH012 to the entry inhibitor IC9564.

Journal article Virology · July 1, 2004 The HIV-1 envelope glycoprotein gp120 is the key determinant for the anti-HIV-1 entry activity of IC9564. A T198P mutation in the gp120 of the HIV-1 primary isolate, DH012, drastically increases IC9564 sensitivity, which can be reversed by growing the viru ... Full text Link to item Cite

The sequence of the CA-SP1 junction accounts for the differential sensitivity of HIV-1 and SIV to the small molecule maturation inhibitor 3-O-{3',3'-dimethylsuccinyl}-betulinic acid.

Journal article Retrovirology · June 29, 2004 BACKGROUND: Despite the effectiveness of currently available antiretroviral therapies in the treatment of HIV-1 infection, a continuing need exists for novel compounds that can be used in combination with existing drugs to slow the emergence of drug-resist ... Full text Link to item Cite

Bifunctional anti-human immunodeficiency virus type 1 small molecules with two novel mechanisms of action.

Journal article Antimicrob Agents Chemother · February 2004 A class of betulinic acid derivatives was synthesized to target two critical steps in the human immunodeficiency virus type 1 (HIV-1) replication cycle, entry and maturation. Each mechanism of HIV-1 inhibition is distinct from clinically available anti-HIV ... Full text Link to item Cite

Small-molecule inhibition of human immunodeficiency virus type 1 replication by specific targeting of the final step of virion maturation.

Journal article J Virol · January 2004 Despite the effectiveness of currently available human immunodeficiency virus type 1 (HIV-1) therapies, a continuing need exists for new drugs to treat HIV-1 infection. We investigated the mechanism by which 3-O-[3',3'-dimethylsuccinyl]-betulinic acid (DSB ... Full text Link to item Cite

Neutralization epitopes of the HIV-1 primary isolate DH012.

Journal article Vaccine · July 4, 2003 To study HIV-1 primary isolate neutralization, we have used DH012 as a model to study the immunogenicity of several DH012 immunogens and determine the potential neutralization epitopes in the virus envelope glycoprotein. Previously, we identified that DH01 ... Full text Link to item Cite

Potential drug targets on the HIV-1 envelope glycoproteins, gp120 and gp41.

Journal article Curr Pharm Des · 2003 HIV-1 entry is an attractive target for anti-HIV-1 therapy. However, there are no entry inhibitors approved for the clinical treatment of HIV-1 infection. This is likely to be changed in the near future since promising HIV-1 entry inhibitors, such as T20 a ... Full text Link to item Cite

Anti-AIDS agents 49. Synthesis, anti-HIV, and anti-fusion activities of IC9564 analogues based on betulinic acid.

Journal article J Med Chem · September 12, 2002 The betulinic acid derivative IC9564 inhibits human immunodeficiency virus (HIV)-1 entry. Among a series of IC9564 derivatives, 5 and 20 were the most promising compounds against HIV infection with EC(50) values of 0.33 and 0.46 microM, respectively. Both ... Full text Link to item Cite

Molecular targets of anti-HIV-1 triterpenes.

Journal article Curr Drug Targets Infect Disord · March 2002 Pentacyclic triterpenes have been found in many plants and may be isolated from any part of the plant. Triterpene derivatives were shown to have biological activities including anti-HIV-1 and anti-cancer activities. The modes of action of the anti-HIV-1 tr ... Full text Link to item Cite

The role of the third beta strand in gp120 conformation and neutralization sensitivity of the HIV-1 primary isolate DH012.

Journal article Proc Natl Acad Sci U S A · December 18, 2001 Neutralization of HIV-1 primary isolates has been a tremendous challenge for AIDS vaccine development. Here, we identify a single amino acid change (T198P) in gp120 that alters the neutralization sensitivity of the primary isolate DH012 to antibodies again ... Full text Link to item Cite

Induction and characterization of neutralizing antibodies against a human immunodeficiency virus type 1 primary isolate.

Journal article J Virol · July 2001 Chimpanzees infected with the primary isolate DH012 mount potent neutralizing antibodies. This DH012 neutralizing activity is highly strain specific. Immune sera from guinea pigs immunized with recombinant DH012 gp120 could also neutralize this primary iso ... Full text Link to item Cite

Role of human immunodeficiency virus (HIV) type 1 envelope in the anti-HIV activity of the betulinic acid derivative IC9564.

Journal article Antimicrob Agents Chemother · January 2001 The betulinic acid derivative IC9564 is a potent anti-human immunodeficiency virus (anti-HIV) compound that can inhibit both HIV primary isolates and laboratory-adapted strains. However, this compound did not affect the replication of simian immunodeficien ... Full text Link to item Cite

Monoclonal antibodies that bind to the core of fusion-active glycoprotein 41.

Journal article AIDS Res Hum Retroviruses · December 10, 2000 The heptad repeat regions HR1 and HR2 of HIV-1 gp41 can associate to form heterooligomers through helical coil-coil interactions that are believed to play a key role in virus-induced membrane fusion. The HR1/HR2 complex was proposed to be the core structur ... Full text Link to item Cite

Identification of gp120 regions targeted by a highly potent neutralizing antiserum elicited in a chimpanzee inoculated with a primary human immunodeficiency virus type 1 isolate.

Journal article J Virol · October 2000 We have previously reported that a chimpanzee infected with a primary human immunodeficiency virus type 1 (HIV-1) isolate (HIV-1(DH12)) developed an extremely potent virus-neutralizing antibody. Immunoglobulin G purified from this animal conferred steriliz ... Full text Link to item Cite

Anti-AIDS agents. 34. Synthesis and structure-activity relationships of betulin derivatives as anti-HIV agents.

Journal article J Med Chem · November 5, 1998 Succinyl and 3'-substituted glutaryl betulin derivatives showed stronger anti-HIV activity and higher therapeutic index (TI) values than their dihydrobetulin counterparts, with ratios of 1.2:1 to 15:1 (cf. 7 and 15, 9 and 17, 10 and 18, 11 and 19, and 12 a ... Full text Link to item Cite

Herpesvirus saimiri transformation of HIV type 1 suppressive CD8+ lymphocytes from an HIV type 1-infected asymptomatic individual.

Journal article AIDS Res Hum Retroviruses · April 10, 1998 CD8+ T lymphocytes from HIV+ individuals can potently suppress HIV-1 replication in a noncytolytic manner. This suppression appears to be multifactorial and the molecules contributing have not been fully elucidated. As an approach to this question we used ... Full text Link to item Cite

Anti-AIDS agents--XXVII. Synthesis and anti-HIV activity of betulinic acid and dihydrobetulinic acid derivatives.

Journal article Bioorg Med Chem · December 1997 Two series of lupane-type triterpenoic acid derivatives were synthesized and evaluated for their inhibitory activity against HIV-1 replication in acutely infected H9 cells, based on the fact that betulinic acid (1) and dihydrobetulinic acid (9) were identi ... Full text Link to item Cite

Oligoclonal CD8 lymphocytes from persons with asymptomatic human immunodeficiency virus (HIV) type 1 infection inhibit HIV-1 replication.

Journal article J Infect Dis · October 1995 CD8 lymphocytes from asymptomatic human immunodeficiency virus (HIV) type 1-infected patients can suppress virus production from infected CD4 cells. Suppressive activity is separate and distinct from cytotoxic T lymphocyte (CTL) reactivities and is likely ... Full text Link to item Cite

A molecular clasp in the human immunodeficiency virus (HIV) type 1 TM protein determines the anti-HIV activity of gp41 derivatives: implication for viral fusion.

Journal article J Virol · June 1995 We have previously reported that synthetic peptides representing the leucine zipper domain (DP107) and a second putative helical domain (DP178) of human immunodeficiency virus type 1 (HIV-1) gp41 exhibit potent anti-HIV activity. In this study we have used ... Full text Link to item Cite

SUPPRESSION OF HIV-1 REPLICATION BY PRIMARY AND TRANSFORMED CD8 CELLS

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · January 1, 1995 Link to item Cite

Anti-AIDS agents. 15. Synthesis and anti-HIV activity of dihydroseselins and related analogs.

Journal article J Med Chem · November 11, 1994 Forty-two dihydroseselins based on the structure of suksdorfin (1) were synthesized in order to evaluate their anti-HIV activity. These synthetic derivatives include 3',4'-di-O-acyl- and 3'- or 4'-O-acyl-cis-dihydroseselins (8-21) and 3',4'-trans-dihydrose ... Full text Link to item Cite

CD8+T-LYMPHOCYTE-MEDIATED INHIBITION OF HIV-1 LTR TRANSCRIPTION

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · August 1, 1994 Link to item Cite

CD8+ T lymphocyte-mediated inhibition of HIV-1 long terminal repeat transcription: a novel antiviral mechanism.

Journal article AIDS Res Hum Retroviruses · November 1993 HIV-1 infection evokes a vigorous antiviral response that may participate in resolving the initial peak of plasma viremia and maintenance of the asymptomatic state. CD8+ T lymphocytes of HIV-1-infected individuals play a critical role in the cellular anti- ... Full text Link to item Cite

The role of cytoplasmic deoxycytidine kinase in the mitochondrial effects of the anti-human immunodeficiency virus compound, 2',3'-dideoxycytidine.

Journal article J Biol Chem · February 15, 1992 2',3'-Dideoxycytidine (ddC) is a potent inhibitor of human immunodeficiency virus replication in vitro and shows beneficial effects in AIDS therapy. The compound inhibits mitochondrial DNA (mtDNA) synthesis at a clinically relevant concentration, which cou ... Link to item Cite

Effect of anti-human immunodeficiency virus nucleoside analogs on mitochondrial DNA and its implication for delayed toxicity.

Journal article Mol Pharmacol · May 1991 The anti-human immunodeficiency virus (-HIV) nucleoside analogs azidothymidine (AZT), dideoxycytidine (ddC), dideoxyinosine (ddl), dideoxydidehydrothymidine (D4T), and dideoxydidehydrocytidine (D4C) and the anticancer drug cytosine arabinoside (AraC) were ... Link to item Cite

Delayed cytotoxicity and selective loss of mitochondrial DNA in cells treated with the anti-human immunodeficiency virus compound 2',3'-dideoxycytidine.

Journal article J Biol Chem · July 15, 1989 The compound 2',3'-dideoxycytidine (ddC) is a potent inhibitor of human immunodeficiency virus replication in vitro and is currently in clinical trials for treatment of acquired immunodeficiency syndrome. The compound was found to exert delayed cytotoxicit ... Link to item Cite