Chemistry and structure-activity relationship of HIV-1 integrase inhibitor integracide B and related natural products.
Integracides, 4,4-dimethylergostane triterpenoids, are inhibitors of HIV-1 integrase, a critical enzyme in replication of HIV-1. The chemistry and structure-activity relationship of integracide B and related natural products are described. A charged group, e.g., a sulfate, carboxyl, or amino, is required for the HIV-1 integrase activity. These compounds showed HIV-1 integrase activity with IC(50) values in the range 4.8-15 muM and exhibited antiviral activity in a viral spread assay, but with only a small or no therapeutic window.
Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. sheo_singh@merck.com
Sheo B
SB
Singh
John G
JG
Ondeyka
William A
WA
Schleif
Peter
P
Felock
Daria J
DJ
Hazuda
D019380:Anti-HIV Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D014315:Triterpenes; C481037:integracide A; C481036:integracide B; D019427:HIV Integrase