title: Pyrrolidinone and pyrrolidine derivatives: Evaluation as inhibitors of InhA and Mycobacterium tuberculosis.
abstract: A series of GEQ analogues bearing pyrrolidinone or pyrrolidine cores were synthesized and evaluated against InhA, essential target for Mycobacterium tuberculosis (M.tb) survival. The compounds were also evaluated against M.tb H37Rv growth. Interestingly, some of the compounds, not efficient as InhA inhibitors, are active against M.tb with MICs up to 1.4 μM. In particular, compound 4b was screened with different M.tb mutated strains in order to identify the cellular target, but without success, suggesting a new possible mode of action.
authors.affiliation: Taras Shevchenko National University of Kyiv, Department of Chemistry, 64 Str. Volodymyrska, Kyiv, 01033, Ukraine; 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.
authors.forename: Tetiana
authors.initials: T
authors.lastname: Matviiuk
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, Mlynskádolina Ch-1, 842 15, Bratislava, Slovakia.
authors.forename: Jan
authors.initials: J
authors.lastname: Madacki
authors.affiliation: University of Pavia, Dipartimento di Biologia e Biotecnologie "Lazzaro Spallanzani", via Ferrata 1, 27100, Pavia, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Mori
authors.affiliation: University of Pavia, Dipartimento di Biologia e Biotecnologie "Lazzaro Spallanzani", via Ferrata 1, 27100, Pavia, Italy.
authors.forename: Beatrice Silvia
authors.initials: BS
authors.lastname: Orena
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.
authors.forename: Christophe
authors.initials: C
authors.lastname: Menendez
authors.affiliation: Taras Shevchenko National University of Kyiv, Department of Chemistry, 64 Str. Volodymyrska, Kyiv, 01033, Ukraine.
authors.forename: Andrii
authors.initials: A
authors.lastname: Kysil
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.
authors.forename: Christiane
authors.initials: C
authors.lastname: André-Barrès
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.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rodriguez
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, Mlynskádolina Ch-1, 842 15, Bratislava, Slovakia.
authors.forename: Jana
authors.initials: J
authors.lastname: Korduláková
authors.affiliation: Université de Toulouse, UPS, Service Commun Rayons X, ICT-FR2599, 118 Route de Narbonne, F-31062, Toulouse cedex 09, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Mallet-Ladeira
authors.affiliation: Taras Shevchenko National University of Kyiv, Department of Chemistry, 64 Str. Volodymyrska, Kyiv, 01033, Ukraine.
authors.forename: Zoia
authors.initials: Z
authors.lastname: Voitenko
authors.affiliation: University of Pavia, Dipartimento di Biologia e Biotecnologie "Lazzaro Spallanzani", via Ferrata 1, 27100, Pavia, Italy.
authors.forename: Maria Rosalia
authors.initials: MR
authors.lastname: Pasca
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. Electronic address: christian.lherbet@itav.fr.
authors.forename: Christian
authors.initials: C
authors.lastname: Lherbet
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. Electronic address: baltas@chimie.ups-tlse.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Baltas
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D026901:Membrane Transport Proteins / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011759:Pyrrolidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D026901:Membrane Transport Proteins; C000599913:MmpL3 protein, Mycobacterium tuberculosis; D011759:Pyrrolidines; D011760:Pyrrolidinones; D010088:Oxidoreductases; C085257:InhA protein, Mycobacterium
keywords: InhA; Inhibition; Mycobacterium tuberculosis; Pyrrolidine; Pyrrolidinone; Synthesis