Imidazoquinoline Derivatives as Potential Inhibitors of InhA Enzyme and <i>Mycobacterium tuberculosis</i>
Pascal Hoffmann,
Joëlle Azéma-Despeyroux,
Fernanda Goncalves,
Alessandro Stamilla,
Nathalie Saffon-Merceron,
Frédéric Rodriguez,
Giulia Degiacomi,
Maria Rosalia Pasca,
Christian Lherbet
Affiliations
Pascal Hoffmann
Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique (SPCMIB), UMR5068, CNRS, Université Paul Sabatier Toulouse III, 31062 Toulouse, France
Joëlle Azéma-Despeyroux
Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique (SPCMIB), UMR5068, CNRS, Université Paul Sabatier Toulouse III, 31062 Toulouse, France
Fernanda Goncalves
Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique (SPCMIB), UMR5068, CNRS, Université Paul Sabatier Toulouse III, 31062 Toulouse, France
Alessandro Stamilla
Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, Italy
Nathalie Saffon-Merceron
Institut de Chimie de Toulouse, ICT-UAR2599, Université Paul Sabatier Toulouse III, 31062 Toulouse, France
Frédéric Rodriguez
Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique (SPCMIB), UMR5068, CNRS, Université Paul Sabatier Toulouse III, 31062 Toulouse, France
Giulia Degiacomi
Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, Italy
Maria Rosalia Pasca
Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, Italy
Christian Lherbet
Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique (SPCMIB), UMR5068, CNRS, Université Paul Sabatier Toulouse III, 31062 Toulouse, France
Tuberculosis is a serious public health problem worldwide. The search for new antibiotics has become a priority, especially with the emergence of resistant strains. A new family of imidazoquinoline derivatives, structurally analogous to triazolophthalazines, which had previously shown good antituberculosis activity, were designed to inhibit InhA, an essential enzyme for Mycobacterium tuberculosis survival. Over twenty molecules were synthesized and the results showed modest inhibitory efficacy against the protein. Docking experiments were carried out to show how these molecules could interact with the protein’s substrate binding site. Disappointingly, unlike triazolophthlazines, these imidazoquinoline derivatives showed an absence of inhibition on mycobacterial growth.
