title: Design, chemical synthesis of 3-(9H-fluoren-9-yl)pyrrolidine-2,5-dione derivatives and biological activity against enoyl-ACP reductase (InhA) and Mycobacterium tuberculosis.
abstract: We report here the discovery, synthesis and screening results of a series of 3-(9H-fluoren-9-yl)pyrrolidine-2,5-dione derivatives as a novel class of potent inhibitors of Mycobacterium tuberculosis H37Rv strain as well as the enoyl acyl carrier protein reductase (ENR) InhA. Among them, several compounds displayed good activities against InhA which is one of the key enzymes involved in the type II fatty acid biosynthesis pathway of the mycobacteria cell wall. Furthermore, some exhibited promising activities against M. tuberculosis and multi-drug resistant M. tuberculosis strains.
authors.affiliation: CNRS, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, LSPCMIB, UMR-5068, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; Université de Toulouse, UPS, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, LSPCMIB, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; Taras Shevchenko National University of Kyiv, Department of Chemistry, 64 Str. Volodymyrska, Kyiv 01033, Ukraine.
authors.forename: Tetiana
authors.initials: T
authors.lastname: Matviiuk
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rodriguez
authors.forename: Nathalie
authors.initials: N
authors.lastname: Saffon
authors.forename: Sonia
authors.initials: S
authors.lastname: Mallet-Ladeira
authors.forename: Marian
authors.initials: M
authors.lastname: Gorichko
authors.forename: Ana Luisa
authors.initials: AL
authors.lastname: de Jesus Lopes Ribeiro
authors.forename: Maria Rosalia
authors.initials: MR
authors.lastname: Pasca
authors.forename: Christian
authors.initials: C
authors.lastname: Lherbet
authors.forename: Zoia
authors.initials: Z
authors.lastname: Voitenko
authors.forename: Michel
authors.initials: M
authors.lastname: Baltas
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011760:Pyrrolidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C000591458:3-(9H-fluoren-9-yl)pyrrolidine-2,5-dione; D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D011760:Pyrrolidinones; D010088:Oxidoreductases; C085257:InhA protein, Mycobacterium
keywords: 3-(9H-Fluoren-9-yl)pyrrolidine-2,5-dione; InhA; Inhibition; Mycobacterium tuberculosis; Succinimide