title: Dicaffeoyl- or digalloyl pyrrolidine and furan derivatives as HIV integrase inhibitors.
abstract: Human immunodeficiency virus (HIV) integrase (IN) catalyzes the integration of HIV DNA copy into the host cell DNA. Such integration is essential for the production of progeny viruses, and therefore therapeutic agents that can inhibit this process should be effective anti-HIV agents. We have previously reported the inhibitory activity of dicaffeoylglucosides against HIV IN. In the present study, we have synthesized and tested dicaffeoyl or digalloyl compounds joined through a five-membered heterocyclic ring as HIV IN inhibitors to explore the SARs of this family of compounds. The starting heterocyclic diols were prepared from L-tartaric acid, diethyl L-tartarate or D-(+)-ribonic gamma-lactone. We found that the HIV IN inhibitory activities of dicaffeoyl derivatives were comparable to that of L-chicoric acid (IC(50)=24.9 microM). On the other hand, digalloyl derivatives were more potent than L-chicoric acid with IC(50) values of 4.7--15.6 microM.
authors.affiliation: Division of Life Sciences, Korea Institute of Science & Technology, PO Box 131, Cheongryang, Seoul 130-650, South Korea.
authors.forename: D J
authors.initials: DJ
authors.lastname: Hwang
authors.forename: S N
authors.initials: SN
authors.lastname: Kim
authors.forename: J H
authors.initials: JH
authors.lastname: Choi
authors.forename: Y S
authors.initials: YS
authors.lastname: Lee
mesh_terms: D002109:Caffeic Acids; D004353:Drug Evaluation, Preclinical; D005663:Furans / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000201:enzymology; D020128:Inhibitory Concentration 50; D011759:Pyrrolidines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013386:Succinates / Q000494:pharmacology
chemical_list: D002109:Caffeic Acids; D005663:Furans; D019428:HIV Integrase Inhibitors; D011759:Pyrrolidines; D013386:Succinates; C032519:pyrrolidine; C100435:chicoric acid; C039281:furan