1. Anti-AIDS agents 87. New bio-isosteric dicamphanoyl-dihydropyranochromone (DCP) and dicamphanoyl-khellactone (DCK) analogues with potent anti-HIV activity.
- Author
-
Liu HS, Xu SQ, Cheng M, Chen Y, Xia P, Qian K, Xia Y, Yang ZY, Chen CH, Morris-Natschke SL, and Lee KH
- Subjects
- Anti-HIV Agents chemistry, Camphor chemistry, Camphor pharmacology, Cell Line, Chromones chemistry, Chromones metabolism, Chromones pharmacology, Coumarins chemistry, Coumarins metabolism, Coumarins pharmacology, Drug Evaluation, Preclinical, HIV Infections drug therapy, HIV Infections virology, HIV-1 drug effects, Humans, Hydroxylation, Inhibitory Concentration 50, Lymphocytes metabolism, Lymphocytes virology, Stereoisomerism, Structure-Activity Relationship, Virus Replication drug effects, Virus Replication physiology, Anti-HIV Agents chemical synthesis, Anti-HIV Agents pharmacology, Camphor analogs & derivatives, Camphor chemical synthesis, Chromones chemical synthesis, Coumarins chemical synthesis, Drug Design
- Abstract
Six 3'R,4'R-di-O-(S)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) and two 3'R,4'R-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives were designed, synthesized, and evaluated for inhibition of HIV-1(NL4-3) replication in TZM-bl cells. 2-Ethyl-2'-monomethyl-1'-oxa- and -1'-thia-DCP (5a, 6a), as well as 2-ethyl-1'-thia-DCP (7a) exhibited potent anti-HIV activity with EC(50) values of 30, 38 and 54 nM and therapeutic indexes of 152.6, 48.0 and 100.0, respectively, which were better than or comparable to those of the lead compound 2-ethyl-DCP in the same assay. 4-Methyl-1'-thia-DCK (8a) also showed significant inhibitory activity with an EC(50) of 128 nM and TI of 237.9., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF