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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.

Publication ,  Journal Article
Zhou, T; Shi, Q; Chen, C-H; Huang, L; Ho, P; Morris-Natschke, SL; Lee, K-H
Published in: 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 (RTMDR-1) strains. Twenty-four DCX analogs (6-29) were synthesized and evaluated against the non-drug-resistant HIV-1 NL4-3 strain, and selected analogs were also screened for their ability to inhibit the RTMDR-1 strain. Compared with the control 2-ethyl-3',4'-di-O-(-)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (2-EDCP, 2), one of the best anti-HIV coumarin derivatives in our prior study, three DCX compounds (7, 12, and 22) showed better activity against both HIV strains with an EC(50) range of 0.062-0.081 μM, and five additional compounds (8, 11, 16, 18, and 21) exhibited comparable anti-HIV potency. Six DCX analogs (7, 11-12, 18, and 21-22) also showed enhanced selectivity index (SI) values in comparison to the control. Structure-activity relationship (SAR) information suggested that the extended conjugated system of the pyranoxanthone skeleton facilitates the interaction of the small DCX molecule within the viral binding pocket, consequently leading to enhanced anti-HIV activity and selectivity. Compared to DCP compounds, DCX analogs are a more promising new class of anti-HIV agents.

Duke Scholars

Published In

Eur J Med Chem

DOI

EISSN

1768-3254

Publication Date

January 2012

Volume

47

Issue

1

Start / End Page

86 / 96

Location

France

Related Subject Headings

  • Xanthenes
  • Medicinal & Biomolecular Chemistry
  • HIV-1
  • Drug Resistance, Viral
  • Drug Design
  • Camphor
  • Anti-HIV Agents
  • 3405 Organic chemistry
  • 3404 Medicinal and biomolecular chemistry
  • 3214 Pharmacology and pharmaceutical sciences
 

Citation

APA
Chicago
ICMJE
MLA
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Zhou, T., Shi, Q., Chen, C.-H., Huang, L., Ho, P., Morris-Natschke, S. L., & Lee, K.-H. (2012). 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. Eur J Med Chem, 47(1), 86–96. https://doi.org/10.1016/j.ejmech.2011.10.025
Zhou, Ting, Qian Shi, Chin-Ho Chen, Li Huang, Phong Ho, Susan L. Morris-Natschke, and Kuo-Hsiung Lee. “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.Eur J Med Chem 47, no. 1 (January 2012): 86–96. https://doi.org/10.1016/j.ejmech.2011.10.025.
Zhou, Ting, et al. “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.Eur J Med Chem, vol. 47, no. 1, Jan. 2012, pp. 86–96. Pubmed, doi:10.1016/j.ejmech.2011.10.025.
Journal cover image

Published In

Eur J Med Chem

DOI

EISSN

1768-3254

Publication Date

January 2012

Volume

47

Issue

1

Start / End Page

86 / 96

Location

France

Related Subject Headings

  • Xanthenes
  • Medicinal & Biomolecular Chemistry
  • HIV-1
  • Drug Resistance, Viral
  • Drug Design
  • Camphor
  • Anti-HIV Agents
  • 3405 Organic chemistry
  • 3404 Medicinal and biomolecular chemistry
  • 3214 Pharmacology and pharmaceutical sciences