title: Anti-mycobacterial activities of some cationic and anionic calix[4]arene derivatives.
abstract: Various polycharged calix[4]arenes were assayed as anti-mycobacterial agents against Mycobacterium tuberculosis, H(37)Rv strain. The sulfonate, carboxylate and phosphonate anionic species displayed no activity. Cationic derivatives integrating four aminoethyl groups at the upper rim and two 6,6'-dimethyl-2,2'-bipyridyl- or 4,4'-dimethyl-2,2'-bithiazolyl subunits at the lower rim were also found inactive against M. tuberculosis, while the unsubstituded and the 5,5'-dimethyl-2,2'-bipyridyl-analogues exhibited MIC values of 3.2 and 0.8μM respectively. Introduction of guanidinoethyl groups at the upper rim resulted, except for the 6,6'-dimethyl-2,2'-bipyridyl-derivative, in high anti-mycobacterial activities for the unsubstituted, the 5,5'-dimethyl-2,2'-bipyridyl- and the 4,4'-dimethyl-2,2'-bithiazolyl analogues, with MIC values of 0.8, 0.8 and 1.6μM, respectively, similar to those of current commercial anti-tuberculosis agents. The five more active substances were also evaluated against the isoniazid-resistant strain MYC5165, resulting in highly interesting micromolar or sub-micromolar MIC and IC(50), ca. 4-125 times more active than isoniazid. These preliminary results are attractive for the development of new anti-TB agents.
authors.affiliation: SRSMC, UMR 7565 Nancy Université, CNRS Groupe d'Etude des Vecteurs Supramoléculaires du Médicament, Faculté de Pharmacie, 5, Rue Albert Lebrun, BP 80403, 54001 Nancy Cedex, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Mourer
authors.forename: Hugues
authors.initials: H
authors.lastname: Massimba Dibama
authors.forename: Patricia
authors.initials: P
authors.lastname: Constant
authors.forename: Mamadou
authors.initials: M
authors.lastname: Daffé
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Regnouf-de-Vains
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry / Q000494:pharmacology; D000838:Anions / Q000737:chemistry / Q000494:pharmacology; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology*; D047250:Calixarenes / Q000737:chemistry* / Q000494:pharmacology*; D019791:Guanidine / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000838:Anions; D000995:Antitubercular Agents; D010636:Phenols; D000644:Quaternary Ammonium Compounds; C121325:calix(4)arene; D047250:Calixarenes; D015082:2,2'-Dipyridyl; D019791:Guanidine