title: Guanidinium compounds with sub-micromolar activities against Mycobacterium tuberculosis. Synthesis, characterization and biological evaluations.
abstract: Seven polycharged species, incorporating 1, 2, 3, 4 and 6 guanidine arms organized around a benzene core were synthesized and assayed as anti-mycobacterial agents against Mycobacterium tuberculosis. They display MIC values comprised between 25 and 12.5 μM (close to ethambutol EMB) for the mono- and the hexa-substituted derivatives, and 0.8 μM (close to isoniazid and streptomycin) for the tri-substituted derivative. The three bi- and the tetra-substituted analogs displayed MIC values of ca. 6.5-3.0 μM. The latter were also evaluated against the isoniazid-resistant MYC5165 strain, resulting in highly interesting micromolar or sub-micromolar MIC, ca. 4-125 times more active than isoniazid. These preliminary results are attractive for the development of new anti-TB agents.
authors.affiliation: CNRS, SRSMC, UMR 7565, équipe MoBAT, F-54506, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Massimba-Dibama
authors.affiliation: CNRS, SRSMC, UMR 7565, équipe MoBAT, F-54506, France; Université de Lorraine, SRSMC, UMR 7565, équipe MoBAT, Vandœuvre-lès-Nancy F-54506, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Mourer
authors.affiliation: CNRS, IPBS (Institut de Pharmacologie et Biologie Structurale), Département Mécanismes Moléculaires des Infections Mycobactériennes, 205 route de Narbonne, F-31077 Toulouse Cedex 04, France; Université de Toulouse, UPS, 118 route de Narbonne, F-31062 Toulouse Cedex 9, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Constant
authors.affiliation: CNRS, IPBS (Institut de Pharmacologie et Biologie Structurale), Département Mécanismes Moléculaires des Infections Mycobactériennes, 205 route de Narbonne, F-31077 Toulouse Cedex 04, France; Université de Toulouse, UPS, 118 route de Narbonne, F-31062 Toulouse Cedex 9, France.
authors.forename: Mamadou
authors.initials: M
authors.lastname: Daffé
authors.affiliation: CNRS, SRSMC, UMR 7565, équipe MoBAT, F-54506, France; Université de Lorraine, SRSMC, UMR 7565, équipe MoBAT, Vandœuvre-lès-Nancy F-54506, France. Electronic address: jean-bernard.regnouf@univ-lorraine.fr.
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Regnouf-de-Vains
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology*; D019791:Guanidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D019791:Guanidine
keywords: Ammonium; Anti-mycobacterial; Guanidinium; Mycobacterium tuberculosis; Tuberculosis