title: Synthesis and HIV-1 inhibitory activities of dicaffeoyl and digalloyl esters of quinic acid derivatives.
abstract: Twenty analogues of the anti-HIV-1 integrase (IN) inhibitors dicaffeoylquinic acids (DCQAs) were prepared. Their IC(50) values for 3'-end processing and strand transfer against recombinant HIV-1IN were determined in vitro, and their cell toxicities and EC(50) against HIV-1 were measured in cells (ex vivo). Acetylated or benzylated and/or with cyclohexylidene group compounds exhibited no inhibition of integration in biochemical assays or viral replication in HIV-infected cells, with the exception of 16 and 36. Removal of these groups, however, correlated with potent inhibition. Compounds 19, 31, and 38, all digalloyls, exhibited the most robust inhibitory performance in biochemical assays as well as in cell culture and less toxicity than other molecules in the current study.
authors.affiliation: Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil.
authors.forename: C O R
authors.initials: CO
authors.lastname: Junior
authors.forename: S C
authors.initials: SC
authors.lastname: Verde
authors.forename: C A M
authors.initials: CA
authors.lastname: Rezende
authors.forename: W
authors.initials: W
authors.lastname: Caneschi
authors.forename: M R C
authors.initials: MR
authors.lastname: Couri
authors.forename: B R
authors.initials: BR
authors.lastname: McDougall
authors.forename: W E
authors.initials: WE
authors.lastname: Robinson
authors.forename: M V
authors.initials: MV
authors.lastname: de Almeida
mesh_terms: D002460:Cell Line; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008958:Models, Molecular; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019428:HIV Integrase Inhibitors; C472707:caffeoylquinic acid; D011801:Quinic Acid