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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-HIV Agents / chemical synthesis*
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / pharmacology*
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Camphor / analogs & derivatives*
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Camphor / chemical synthesis*
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Camphor / chemistry
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Camphor / pharmacology
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Cell Line
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Chromones / chemical synthesis*
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Chromones / chemistry
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Chromones / metabolism
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Chromones / pharmacology
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Coumarins / chemical synthesis*
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Coumarins / chemistry
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Coumarins / metabolism
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Coumarins / pharmacology
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Drug Design*
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Drug Evaluation, Preclinical
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HIV Infections / drug therapy
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HIV Infections / virology
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HIV-1 / drug effects
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Humans
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Hydroxylation
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Inhibitory Concentration 50
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Lymphocytes / metabolism
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Lymphocytes / virology
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Stereoisomerism
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Structure-Activity Relationship
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Virus Replication / drug effects
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Virus Replication / physiology
Substances
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Anti-HIV Agents
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Chromones
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Coumarins
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dihydropyranochromone
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Camphor
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khellactone