Catechol-substituted L-chicoric acid analogues as HIV integrase inhibitors

HIV integrase catalyzes the integration of HIV DNA copy into the host cell DNA, which is essential for the production of progeny viruses. L-Chicoric acid and dicaffeoylquinic acids, isolated from plants, are well known potent inhibitors of HIV integrase. The common structural features of these inhibitors are caffeic acid derivatives connected to tartaric acid or quinic acid through ester bonds. In the present study, we have synthesized and tested the inhibitory activities of a new type of HIV IN inhibitors, which has catechol groups in place of caffeoyl groups in the structure of L-chicoric acid. Upon substitution of catechol groups at succinic acid, pyrrol dicarboxylic acid, maleimide or maleic anhydride, the inhibitory activities (IC50 = 3.8-23.6 muM) were retained or remarkably increased when compared to parent compound L-chicoric acid (IC50 = 13.7 muM). (C) 2003 Elsevier Ltd. All rights reserved.