The calanolides, a novel HIV-inhibitory class of coumarin derivatives from the tropical rainforest tree, Calophyllum lanigerum.
24 Jul 1992-Journal of Medicinal Chemistry (American Chemical Society)-Vol. 35, Iss: 15, pp 2735-2743
TL;DR: Calanolide A was active not only against the AZT-resistant G-9106 strain of HIV-1 but also against the pyridinone-resistant A17 strain, which was of particular interest since the A17 virus is highly resistant to previously known HIV- 1 specific, non-nucleoside RT inhibitors.
Abstract: Eight new coumarin compounds (1-8) were isolated by anti-HIV bioassay-guided fractionation of an extract of Calophyllum lanigerum. The structures of calanolide A (1), 12-acetoxycalanolide A (2), 12-methoxycalanolide A (3), calanolide B (4), 12-methoxycalanolide B (5), calanolide C (6) and related derivatives 7 and 8 were solved by extensive spectroscopic analyses, particularly HMQC, HMBC, and difference NOE NMR experiments. The absolute stereochemistry of calanolide A (1) and calanolide B (4) was established by a modified Mosher's method. Calanolides A (1) and B (4) were completely protective against HIV-1 replication and cytopathicity (EC50 values of 0.1 microM and 0.4 microM, respectively), but were inactive against HIV-2. Some of the related compounds also showed evidence of anti-HIV-1 activity. Studies with purified bacterial recombinant reverse transcriptases (RT) revealed that the calanolides are HIV-1 specific RT inhibitors. Moreover, calanolide A was active not only against the AZT-resistant G-9106 strain of HIV-1 but also against the pyridinone-resistant A17 strain. This was of particular interest since the A17 virus is highly resistant to previously known HIV-1 specific, non-nucleoside RT inhibitors (e.g., TIBO; BI-RG-587; L693,593) which comprise a structurally diverse but apparently common pharmacologic class. The calanolides represent a substantial departure from the known class and therefore provide a novel new anti-HIV chemotype for drug development.
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Cites background from "The calanolides, a novel HIV-inhibi..."
...Stevens (Clusiaceae), a Malaysian rainforest tree (Kashman et al., 1992; Yang et al., 2001; Yu et al., 2003)....
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...1) is a dipyranocoumarin natural product isolated from Calophyllum lanigerum var. austrocoriaceum (Whitmore) P.F. Stevens (Clusiaceae), a Malaysian rainforest tree (Kashman et al., 1992; Yang et al., 2001; Yu et al., 2003)....
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