title: Alkylamino derivatives of pyrazinamide: synthesis and antimycobacterial evaluation.
abstract: A series of pyrazinamide derivatives with alkylamino substitution was designed, synthesized and tested for their ability to inhibit the growth of selected mycobacterial, bacterial and fungal strains. The target structures were prepared from the corresponding 5-chloro (1) or 6-chloropyrazine-2-carboxamide (2) by nucleophilic substitution of chlorine by various non-aromatic amines (alkylamines). To determine the influence of alkyl substitution, corresponding amino derivatives (1a, 2a) and compounds with phenylalkylamino substitution were prepared. Some of the compounds exerted antimycobacterial activity against Mycobacterium tuberculosis H37Rv significantly better than standard pyrazinamide and corresponding starting compounds (1 and 2). Basic structure-activity relationships are presented. Only weak antibacterial and no antifungal activity was detected.
authors.affiliation: Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové 500 05, Czech Republic. Electronic address: barbora.servusova@faf.cuni.cz.
authors.forename: Barbora
authors.initials: B
authors.lastname: Servusová
authors.affiliation: Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové 500 05, Czech Republic.
authors.forename: Pavla
authors.initials: P
authors.lastname: Paterová
authors.affiliation: Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové 500 05, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Mandíková
authors.affiliation: Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové 500 05, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Kubíček
authors.affiliation: Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové 500 05, Czech Republic.
authors.forename: Radim
authors.initials: R
authors.lastname: Kučera
authors.affiliation: Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové 500 05, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Kuneš
authors.affiliation: Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové 500 05, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Doležal
authors.affiliation: Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové 500 05, Czech Republic. Electronic address: jan.zitko@faf.cuni.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Zitko
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000494:pharmacology; D003461:Crystallography; D004353:Drug Evaluation, Preclinical / Q000379:methods; D056945:Hep G2 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000502:physiology; D011718:Pyrazinamide / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000995:Antitubercular Agents; D011718:Pyrazinamide
keywords: 5-Chloropyrazine-2-carboxamide; 6-Chloropyrazine-2-carboxamide; Alkylamines; Antimycobacterial activity; Cytotoxicity