Structure-activity modifications of the HIV-1 inhibitors (+)-calanolide A and (-)-calanolide B.
The delta 7,8 olefinic linkages within (+)-calanolide A(1) and (-)-calanolide B(2) were catalytically reduced to determine impact on the anti-HIV activity of the parent compounds. In addition, a series of structure modifications of the C-12 hydroxyl group in (-)-calanolide B was made to investigate the importance of that substituent to the HIV-1 inhibitory activity of these coumarins. A total of 14 analogs were isolated or prepared and compared to (+)-calanolide A and (-)-calanolide B in the NCI primary anti-HIV assay. While none of the compounds showed activity superior to the two unmodified leads, some structure-activity requirements were apparent from the relative anti-HIV potencies of the various analogs.
Laboratory of Drug Discovery Research and Development, National Cancer Institute, Frederick, Maryland 21702-1201, USA.
D L
DL
Galinis
R W
RW
Fuller
T C
TC
McKee
J H
JH
Cardellina
R J
RJ
Gulakowski
J B
JB
McMahon
M R
MR
Boyd
D019380:Anti-HIV Agents / Q000737:chemistry*; D000998:Antiviral Agents / Q000737:chemistry*; D003374:Coumarins / Q000737:chemistry*; D003588:Cytopathogenic Effect, Viral; D006801:Humans; D039681:Pyranocoumarins; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D003374:Coumarins; D039681:Pyranocoumarins; C075958:calanolide B; C075959:calanolide A