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

Journal Article (Journal Article)

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 screened against HIV-1(NL4-3) and a multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR) strain in the TZM-bl cell line, using seco-DCK (7) and 2-ethyl-DCP (4) as controls. Several compounds (14, 18, 19, 22-24, and 32) exhibited potent anti-HIV activity with EC(50) values ranging from 0.93 to 1.93 μM and therapeutic index (TI) values ranging from 20 to 39. 1'-O-Isopropoxy-2',3'-seco-3'-nor-DCP (12) showed the greatest potency among the newly synthesized compounds with EC(50) values of 0.47 and 0.88 μM, and TI of 96 and 51, respectively, against HIV-1(NL4-3) and RTMDR strains. The seco-compounds exhibited better chemical stability in acidic conditions compared with DCP and DCK compounds. Overall, the results suggested that seco-DCP analogues with simplified structures may be more favorable for development as novel anti-HIV candidates.

Full Text

Duke Authors

Cited Authors

  • Chen, Y; Cheng, M; Liu, F-Q; Xia, P; Qian, K; Yu, D; Xia, Y; Yang, Z-Y; Chen, C-H; Morris-Natschke, SL; Lee, K-H

Published Date

  • October 2011

Published In

Volume / Issue

  • 46 / 10

Start / End Page

  • 4924 - 4936

PubMed ID

  • 21864952

Pubmed Central ID

  • 21864952

Electronic International Standard Serial Number (EISSN)

  • 1768-3254

Digital Object Identifier (DOI)

  • 10.1016/j.ejmech.2011.07.051


  • eng

Conference Location

  • France