Inhibition of human immunodeficiency virus type-1 integrase by curcumin

• Published in: Biochemical pharmacology 1995-04, Vol.49 (8), p.1165-1170
• Main Authors: Mazumder, Abhijit, Raghavan, Krishnamachari, Weinstein, John, Kohn, Kurt W., Pommier, Yves
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Antibiotics. Antiinfectious agents. Antiparasitic agents; antiviral; Antiviral agents; Antiviral Agents - pharmacology; Base Sequence; Binding Sites; Biological and medical sciences; curcumin; Curcumin - pharmacology; DNA Nucleotidyltransferases - antagonists & inhibitors; DNA Nucleotidyltransferases - genetics; Dose-Response Relationship, Drug; HIV-1 - enzymology; human immunodeficiency; human immunodeficiency virus 1; inhibition; integrase; Integrases; Medical sciences; Molecular Sequence Data; Pharmacology. Drug treatments; Structure-Activity Relationship; structureactivity; virus Type-1
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/0006-2952(95)98514-A

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 concentration 50 ( ic 50) for strand transfer of 40 μM. 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.