Anti-AIDS agents. 42. Synthesis and anti-HIV activity of disubstituted (3'R,4'R)-3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone analogues.

Journal Article (Journal Article)

A series of disubstituted 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogues (1-10) were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. 5-Methoxy-4-methyl DCK (8) was the most promising compound with an EC(50) value of 7.21 x 10(-6) microM and a therapeutic index of >2.08 x 10,(7) which were much better than those of lead compound DCK in the same assay. Another six disubstituted DCK analogues (1-5 and 7) were more potent than AZT but less active than DCK. Conformational analysis suggested that resonance of the coumarin system is an essential structural feature for potent anti-HIV activity. Steric compression of C(4) and C(5) substituents of the coumarin moiety can reduce the overall planarity and thus resonance of the coumarin nucleus, resulting in a decrease or lack of anti-HIV activity.

Full Text

Duke Authors

Cited Authors

  • Xie, L; Takeuchi, Y; Cosentino, LM; McPhail, AT; Lee, KH

Published Date

  • March 2001

Published In

Volume / Issue

  • 44 / 5

Start / End Page

  • 664 - 671

PubMed ID

  • 11262077

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

International Standard Serial Number (ISSN)

  • 0022-2623

Digital Object Identifier (DOI)

  • 10.1021/jm000070g


  • eng