title: Synthesis and Antimicrobial Evaluation of 6-Alkylamino-N-phenylpyrazine-2-carboxamides.
abstract: This work presents synthesis and antimicrobial evaluation of nineteen 6-alkylamino-N-phenylpyrazine-2-carboxamides. Antimycobacterial activity was determined against Mycobacterium tuberculosis H37Rv, M. kansasii and two strains of M. avium. Generally, the antimycobacterial activity increased with prolongation of simple alkyl chain and culminated in compounds with heptylamino substitution (3e, 4e) with MIC = 5-10 μm against M. tuberculosis H37Rv. On the contrary, derivatives with modified alkyl chain (containing e.g. terminal methoxy or hydroxy group) as well as phenylalkylamino derivatives were mainly inactive. The most active compounds (with hexyl to octylamino substitution) were evaluated for their in vitro activity against drug-resistant strains of M. tuberculosis and possessed activity comparable to that of the reference drug isoniazid. None of the tested compounds were active against M. avium. Some derivatives exhibited activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (best MIC = 7.8 μm), while Gram-negative strains as well as tested fungal strains were completely unsusceptible. Active compounds were tested for in vitro toxicity on various cell lines and in most cases were non-toxic up to 100 μm.
authors: Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové, 500 05, Czech Republic.
authors: Barbora
authors: B
authors: Servusova-Vanaskova
authors: Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové, 500 05, Czech Republic.|Department of Clinical Microbiology, University Hospital Hradec Králové, Sokolská 581, Hradec Králové, 500 05, Czech Republic.
authors: Pavla
authors: P
authors: Paterova
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojárov 10, Bratislava, 832 32, Slovakia.
authors: Vladimir
authors: V
authors: Garaj
authors: Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové, 500 05, Czech Republic.
authors: Jana
authors: J
authors: Mandikova
authors: Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové, 500 05, Czech Republic.
authors: Jiri
authors: J
authors: Kunes
authors: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, Leuven, 3000, Belgium.
authors: Lieve
authors: L
authors: Naesens
authors: Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové, 500 05, Czech Republic.
authors: Petr
authors: P
authors: Jílek
authors: Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové, 500 05, Czech Republic.
authors: Martin
authors: M
authors: Dolezal
authors: Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové, 500 05, Czech Republic.
authors: Jan
authors: J
authors: Zitko
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D000935:Antifungal Agents; D000995:Antitubercular Agents
keywords: antibacterial evaluation; antimycobacterial evaluation; cytotoxicity; multidrug-resistant strains; pyrazinamide derivatives