Scholars@Duke publication: Aloperine and Its Derivatives as a New Class of HIV-1 Entry Inhibitors.

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

Publication , Journal Article

Dang, Z; Zhu, L; Lai, W; Bogerd, H; Lee, K-H; Huang, L; Chen, C-H

Published in: 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 aloperine derivatives with a variety of N12-substitutions were synthesized. Among them, 12d with an N-(1-butyl)-4-trifluoromethoxy-benzamide side chain showed the most potent anti-HIV-1 activity with EC50 at 0.69 μM. Aloperine derivatives inhibited both X4 and R5 HIV-1 Env-mediated cell-cell fusions. In addition, both BMS-806, a compound representing a class of HIV-1 gp120-targeting small molecules in clinical trials, and resistant and sensitive HIV-1 Env-mediated cell-cell fusions were equally sensitive to aloperine derivatives. These results suggest that aloperine and its derivatives are a new class of anti-HIV-1 entry inhibitors.

Duke Scholars

Author Li Huang Surgery, Surgical Sciences

Author Chin-Ho Chen Surgery, Surgical Sciences

Published In

ACS Med Chem Lett

DOI

10.1021/acsmedchemlett.5b00339

ISSN

1948-5875

Publication Date

March 10, 2016

Volume

Issue

Start / End Page

240 / 244

Location

United States

Related Subject Headings

3405 Organic chemistry
3404 Medicinal and biomolecular chemistry
1115 Pharmacology and Pharmaceutical Sciences
0305 Organic Chemistry
0304 Medicinal and Biomolecular Chemistry

Citation

APA

Chicago

ICMJE

MLA

NLM

Dang, Z., Zhu, L., Lai, W., Bogerd, H., Lee, K.-H., Huang, L., & Chen, C.-H. (2016). Aloperine and Its Derivatives as a New Class of HIV-1 Entry Inhibitors. ACS Med Chem Lett, 7(3), 240–244. https://doi.org/10.1021/acsmedchemlett.5b00339

Dang, Zhao, Lei Zhu, Weihong Lai, Hal Bogerd, Kuo-Hsiung Lee, Li Huang, and Chin-Ho Chen. “Aloperine and Its Derivatives as a New Class of HIV-1 Entry Inhibitors.” ACS Med Chem Lett 7, no. 3 (March 10, 2016): 240–44. https://doi.org/10.1021/acsmedchemlett.5b00339.

Dang Z, Zhu L, Lai W, Bogerd H, Lee K-H, Huang L, et al. Aloperine and Its Derivatives as a New Class of HIV-1 Entry Inhibitors. ACS Med Chem Lett. 2016 Mar 10;7(3):240–4.

Dang, Zhao, et al. “Aloperine and Its Derivatives as a New Class of HIV-1 Entry Inhibitors.” ACS Med Chem Lett, vol. 7, no. 3, Mar. 2016, pp. 240–44. Pubmed, doi:10.1021/acsmedchemlett.5b00339.

Dang Z, Zhu L, Lai W, Bogerd H, Lee K-H, Huang L, Chen C-H. Aloperine and Its Derivatives as a New Class of HIV-1 Entry Inhibitors. ACS Med Chem Lett. 2016 Mar 10;7(3):240–244.

Published In

ACS Med Chem Lett

DOI

10.1021/acsmedchemlett.5b00339

ISSN

1948-5875

Publication Date

March 10, 2016

Volume

Issue

Start / End Page

240 / 244

Location

United States

Related Subject Headings

3405 Organic chemistry
3404 Medicinal and biomolecular chemistry
1115 Pharmacology and Pharmaceutical Sciences
0305 Organic Chemistry
0304 Medicinal and Biomolecular Chemistry