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

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 with an EC(50) value of 0.058 microM and a therapeutic index (TI) of 1000. The activity of 9 was better than that of 4-methyl DCK (2, EC(50): 0.126 microM, TI: 301.2) in the same assay. Additionally, 9 also showed antiviral activity against a multi-RT inhibitor-resistant strain (RTMDR), which is insensitive to most DCK analogs. Compared with 2, compound 9 has a less complex structure, fewer hydrogen-bond acceptors, and a reduced log P value. Therefore, it is likely to exhibit better ADME, and appears to be a promising new lead for further development as an anti-HIV candidate.

Full Text

Duke Authors

Cited Authors

  • Tang, J; Qian, K; Zhang, B-N; Chen, Y; Xia, P; Yu, D; Xia, Y; Yang, Z-Y; Chen, C-H; Morris-Natschke, SL; Lee, K-H

Published Date

  • June 15, 2010

Published In

Volume / Issue

  • 18 / 12

Start / End Page

  • 4363 - 4373

PubMed ID

  • 20537902

Pubmed Central ID

  • 20537902

Electronic International Standard Serial Number (EISSN)

  • 1464-3391

Digital Object Identifier (DOI)

  • 10.1016/j.bmc.2010.04.089


  • eng

Conference Location

  • England