CURCUMIN AND CURCUMIN DERIVATIVES INHIBIT TAT-MEDIATED TRANSACTIVATION OF TYPE-1 HUMAN-IMMUNODEFICIENCY-VIRUS LONG TERMINAL REPEAT

The transcription of HIV1 provirus is regulated by both cellular and v iral factors. Various evidence suggests that Tat protein secreted by H IV1-infected cells may have additional action in the pathogenesis of A IDS because of its ability to also be taken up by non-infected cells. Curcumin [diferuloylmethane or hydroxy-3-methoxyphenyl)-1,6-heptadiene -3,5-dione] is the yellow pigment in turmeric Curcuma longa (Linn). it exhibits a variety of pharmacological effects including antiinflammat ory and antiretroviral activities. Here, we demonstrated that curcumin used at 10 to 100 nM inhibited Tat transactivation of HIV1-LTR lacZ b y 70 to 80% in HeLa cells. In order to develop more efficient curcumin derivatives, we synthesized and tested in the same experimental syste m the inhibitory activity of reduced curcumin (C-1), which lacks the s patial structure of curcumin; allyl-curcumin (C-2), which possesses a condensed allyl derivative on curcumin that plays the role of metal ch elator; and tocopheryl-curcumin (C-3), which enhances the antioxidant activity of the molecule. Results obtained with C-1, C-2 and C-3 curcu min derivatives showed a significant inhibition (70 to 85%) of Tat tra nsactivation. Despite the fact that tocopheryl-curcumin (C-3) failed t o scavenge O-2(.-), this curcumin derivative exhibited the most activi ty; 70% inhibition was obtained at 1 nM, while only 35% inhibition was obtained with the curcumin.