title: Catechol-substituted L-chicoric acid analogues as HIV integrase inhibitors.
abstract: 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, pyrrole-dicarboxylic acid, maleimide or maleic anhydride, the inhibitory activities (IC(50)=3.8-23.6 microM) were retained or remarkably increased when compared to parent compound L-chicoric acid (IC(50)=13.7 microM).
authors.affiliation: Division of Life Sciences, Korea Institute of Science & Technology, PO Box 131, Cheongryang, Seoul 130-650, South Korea.
authors.forename: Jae Yeol
authors.initials: JY
authors.lastname: Lee
authors.forename: Kwon Joong
authors.initials: KJ
authors.lastname: Yoon
authors.forename: Yong Sup
authors.initials: YS
authors.lastname: Lee
mesh_terms: D002109:Caffeic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D002396:Catechols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019427:HIV Integrase / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D010936:Plant Extracts / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013386:Succinates / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D002109:Caffeic Acids; D002396:Catechols; D019428:HIV Integrase Inhibitors; D010936:Plant Extracts; D013386:Succinates; D019427:HIV Integrase; C100435:chicoric acid