Inhibition of human immunodeficiency virus type-1 integrase by curcumin.
Curcumin (diferuloylmethane) is the yellow pigment in turmeric (Curcuma longa L.) that is widely used as a spice, food coloring (curry) and preservative. Curcumin exhibits a variety of pharmacological effects including antitumor, anti-inflammatory, and anti-infectious activities and is currently in clinical trials for AIDS patients. The effects of curcumin have been determined on purified human immunodeficiency virus type 1 (HIV-1) integrase. Curcumin has an inhibitory concentration50 (IC50) for strand transfer of 40 microM. Inhibition of an integrase deletion mutant containing only amino acids 50-212 suggests that curcumin interacts with the integrase catalytic core. Two structural analogs, methyl cinnamate and chlorogenic acid, were inactive. Energy minimization studies suggest that the anti-integrase activity of curcumin could be due to an intramolecular stacking of two phenyl rings that brings the hydroxyl groups into close proximity. The present data suggest that HIV-1 integrase inhibition may contribute to the antiviral activity of curcumin. These observations suggest new strategies for antiviral drug development that could be based upon curcumin as a lead compound for the development of inhibitors of HIV-1 integrase.
Mazumder
A
A
Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892-4255, USA.
Raghavan
K
K
Weinstein
J
J
Kohn
K W
KW
Pommier
Y
Y
D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D003474:Curcumin / Q000494:pharmacology*; D004254:DNA Nucleotidyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000201:enzymology*; D019426:Integrases; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D004254:DNA Nucleotidyltransferases; D019426:Integrases; D003474:Curcumin