Synthesis and evaluation of β-hydroxytriazoles and related compounds as antitubercular agents

Authors

  • Christophe Menendez CNRS; Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, SPCMIB, 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, SPCMIB; 118 route de Narbonne, F-31062 Toulouse cedex 9, France
  • Giorgia Mori University of Pavia, Dipartimento di Biologia e Biotecnologie “Lazzaro Spallanzani”, via Ferrata 1, 27100 Pavia, Italy
  • Mathilde Maillot CNRS; Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, SPCMIB, 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, SPCMIB; 118 route de Narbonne, F-31062 Toulouse cedex 9, France
  • Isabelle Fabing CNRS; Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, SPCMIB, 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, SPCMIB; 118 route de Narbonne, F-31062 Toulouse cedex 9, France
  • Chantal Carayon CNRS; Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, SPCMIB, 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, SPCMIB; 118 route de Narbonne, F-31062 Toulouse cedex 9, France
  • Béatrice Silvia Orena University of Pavia, Dipartimento di Biologia e Biotecnologie “Lazzaro Spallanzani”, via Ferrata 1, 27100 Pavia, Italy
  • Maria Rosalia Pasca University of Pavia, Dipartimento di Biologia e Biotecnologie “Lazzaro Spallanzani”, via Ferrata 1, 27100 Pavia, Italy
  • Zoia Voitenko Taras Shevchenko National University of Kyiv, Department of Chemistry, 64 str. Volodymyrska, Kyiv, 01033, Ukraine
  • Christian Lherbet CNRS; Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, SPCMIB, 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, SPCMIB; 118 route de Narbonne, F-31062 Toulouse cedex 9, France
  • Michel Baltas CNRS; Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, SPCMIB, 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, SPCMIB; 118 route de Narbonne, F-31062 Toulouse cedex 9, France

DOI:

https://doi.org/10.17721/fujcV3I1P82-96

Keywords:

Mycobacterium tuberculosis, β-hydroxytriazole, α, β-diketotriazole, oxidation, IBX, inhibition

Abstract


A new series of β-hydroxytriazoles were synthesized and evaluated as Mycobacterium tuberculosis inhibitors. Our strategy implied the synthesis of alkyne precursors through a Barbier reaction between benzaldehydes and propargyl bromide followed by click chemistry to afford substituted β-hydroxyl benzyltriazoles. These compounds are also key intermediates either for oxidation reactions leading to α,β-diketotriazoles or for elimination reactions affording styryl triazoles. Evaluation of all new compounds for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv resulted in compounds with MIC up to 7 μM.

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Published

2015-03-10

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