title: Design, synthesis, and anti-integrase activity of catechol-DKA hybrids.
abstract: Following the discovery of diketoacid-containing compounds as HIV-1 integrase (IN) inhibitors, a plethora of new molecules have been published leading to four drugs under clinical trial. In an attempt to rationally design new dimeric diketoacids (DKAs) targeting two divalent metal ions on the active site of IN, potent inhibitors against purified IN were found with varied selectivity for strand transfer. In this context, we designed and synthesized a new series of catechol-DKA hybrids. These compounds presented micromolar anti-integrase activities with moderate antiviral properties.
authors.affiliation: Laboratoire de Chimie Organique et Macromoléculaire, UMR CNRS 8009, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Maurin
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bailly
authors.forename: Gladys
authors.initials: G
authors.lastname: Mbemba
authors.forename: Jean François
authors.initials: JF
authors.lastname: Mouscadet
authors.forename: Philippe
authors.initials: P
authors.lastname: Cotelle
mesh_terms: D000143:Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002384:Catalysis; D002396:Catechols / Q000737:chemistry*; D019281:Dimerization; D015195:Drug Design; D019427:HIV Integrase / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000143:Acids; D002396:Catechols; D019428:HIV Integrase Inhibitors; D019427:HIV Integrase; C034221:catechol