Synthesis of 3-heteryl substituted pyrrolidine-2,5-diones via catalytic Michael reaction and evaluation of their inhibitory activity against InhA and Mycobacterium tuberculosis

Tetiana Matviiuk; Giorgia Mori; Christian Lherbet; Frédéric Rodriguez; Maria Rosalia Pasca; Marian Gorichko; Brigitte Guidetti; Zoia Voitenko; Michel Baltas

doi:10.1016/j.ejmech.2013.10.069

Synthesis of 3-heteryl substituted pyrrolidine-2,5-diones via catalytic Michael reaction and evaluation of their inhibitory activity against InhA and Mycobacterium tuberculosis

Eur J Med Chem. 2014 Jan:71:46-52. doi: 10.1016/j.ejmech.2013.10.069. Epub 2013 Nov 4.

Authors

Tetiana Matviiuk¹, Giorgia Mori², Christian Lherbet³, Frédéric Rodriguez⁴, Maria Rosalia Pasca², Marian Gorichko⁵, Brigitte Guidetti⁶, Zoia Voitenko⁷, Michel Baltas⁸

Affiliations

¹ 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 01601, Ukraine.
² University of Pavia, Dipartimento di Biologia e Biotecnologie "Lazzaro Spallanzani", via Ferrata 1, 27100 Pavia, Italy.
³ 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; 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. Electronic address: lherbet@chimie.ups-tlse.fr.
⁴ 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; 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.
⁵ Taras Shevchenko National University of Kyiv, Department of Chemistry, 64 str. Volodymyrska, Kyiv 01601, Ukraine.
⁶ 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.
⁷ Taras Shevchenko National University of Kyiv, Department of Chemistry, 64 str. Volodymyrska, Kyiv 01601, Ukraine. Electronic address: z_voitenko@mail.univ.kiev.ua.
⁸ 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; 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. Electronic address: baltas@chimie.ups-tlse.fr.

PMID: 24269516
DOI: 10.1016/j.ejmech.2013.10.069

Abstract

In the present paper, we report the synthesis via catalytic Michael reaction and biological results of a series of 3-heteryl substituted pyrrolidine-2,5-dione derivatives as moderate inhibitors against Mycobacterium tuberculosis H37Rv growth. Some of them present also inhibition activities against InhA.

Keywords: InhA; Michael addition; Succinimide; Tuberculosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antitubercular Agents / chemical synthesis
Antitubercular Agents / chemistry*
Antitubercular Agents / pharmacology*
Bacterial Proteins / antagonists & inhibitors*
Bacterial Proteins / metabolism
Humans
Microbial Sensitivity Tests
Models, Molecular
Mycobacterium tuberculosis / drug effects*
Mycobacterium tuberculosis / growth & development
Oxidoreductases / antagonists & inhibitors*
Oxidoreductases / metabolism
Pyrrolidines / chemical synthesis
Pyrrolidines / chemistry*
Pyrrolidines / pharmacology*
Structure-Activity Relationship
Tuberculosis / drug therapy

Substances

Antitubercular Agents
Bacterial Proteins
Pyrrolidines
Oxidoreductases
InhA protein, Mycobacterium
pyrrolidine