Léa Lecoq

Université Toulouse III - Paul Sabatier

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Giorgia Mori

University of Sydney

Vania Bernardes‐Génisson

Centre National de la Recherche Scientifique

Geneviève Pratviel

Laboratoire de Chimie de Coordination

Jean‐Luc Stigliani

Laboratoire de Chimie de Coordination

Alix Sournia‐Saquet

Laboratoire de Chimie de Coordination

Céline Deraeve

Laboratoire de Chimie de Coordination

Béatrice Silvia Orena

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Julie Laborde

Université de Toulouse

Cooperative Institutions

Centre National de la Recherche Scientifique

Université de Toulouse

Université Toulouse III - Paul Sabatier

Laboratoire de Chimie de Coordination

Institut National Polytechnique de Toulouse

University of Pavia

Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani

University of Puerto Rico at Carolina

Pharmacochimie et Pharmacologie pour le Développement

University of Sydney

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Synthesis, oxidation potential and anti-mycobacterial activity of isoniazid and analogues: insights into the molecular isoniazid activation mechanism

ChemistrySelect (2016)

Julie Laborde Céline Deraeve Léa Lecoq Alix Sournia‐Saquet Jean‐Luc Stigliani

Tuberculosis (TB) is one of the leading causes of death due to infectious diseases. Among the specific drugs currently employed to treat tuberculosis, isoniazid (INH), a pro-drug, attracts a great interest. However, Mycobacterium tuberculosis (MTB) clinical isolates resistant to INH are significantly increasing thus compromising the efficiency of TB-treatment. Concerning the mechanism of resistance to INH, it is nowadays well established that it mainly results from mutations in the katG genes encoding for INH enzymatic activator. Recently, it was proposed that mutation in katG induces differences in heme or side chain redox potential so that the enzyme loses its ability to oxidize INH to radical species. In this work, we synthesized and selected a series of INH analogues for a study of their oxidation potential and evaluation of their anti-TB efficiency toward MTB wild-type and drug resistant strains. On the contrary to what was postulated, no correlation exists between the easier oxidation of a molecule and its anti-MTB activity toward resistant strains. Based on experimental data and theoretical calculations, we proposed an activation mechanism for INH and analogues based on a one-electron oxidation step of the hydrazyl function at the proximal nitrogen followed by a radical transposition to the distal nitrogen, which then induces a β-homolytic cleavage of the C(=O)-N bond to afford diazene and the isonicotinoyl radical species.

10.1002/slct.201600040

Cite

Citations (23)

ChemInform Abstract: Synthesis, Oxidation Potential and anti‐Mycobacterial Activity of Isoniazid and Analogues: Insights into the Molecular Isoniazid Activation Mechanism.

ChemInform (2016)

Julie Laborde Céline Deraeve Léa Lecoq Alix Sournia‐Saquet Jean‐Luc Stigliani

10.1002/chin.201626105

Cite

Citations (0)