title: Novel pyrazine analogs of chalcones: synthesis and evaluation of their antifungal and antimycobacterial activity.
abstract: Infectious diseases, such as tuberculosis and invasive mycoses, represent serious health problems. As a part of our long-term efforts to find new agents for the treatment of these diseases, a new series of pyrazine analogs of chalcones bearing an isopropyl group in position 5 of the pyrazine ring was prepared. The structures of the compounds were corroborated by IR and NMR spectroscopy and their purity confirmed by elemental analysis. The susceptibility of eight fungal strains to the studied compounds was tested. The results have been compared with the activity of some previously reported propyl derivatives. The only strain that was susceptible to the studied compounds was Trichophyton mentagrophytes. It was found that replacing a non-branched propyl with a branched isopropyl did not have a decisive and unequivocal influence on the in vitro antifungal activity against T. mentagrophytes. In vitro activity against Trichophyton mentagrophytes comparable with that of fluconazole was exhibited by nitro-substituted derivatives. Unfortunately, no compound exhibited efficacy comparable with that of terbinafine, which is the most widely used agent for treating mycoses caused by dermatophytes. Some of the prepared compounds were assayed for antimycobacterial activity against M. tuberculosis H37Rv. The highest potency was also displayed by nitro-substituted compounds. The results of the present study are in a good agreement with our previous findings and confirm the positive influence of electron-withdrawing groups on the B-ring of chalcones on the antifungal and antimycobacterial activity of these compounds.
authors.affiliation: Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic. marta.kucerova@faf.cuni.cz.
authors.forename: Marta
authors.initials: M
authors.lastname: Kucerova-Chlupacova
authors.affiliation: Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic. jiri.kunes@faf.cuni.cz.
authors.forename: Jiri
authors.initials: J
authors.lastname: Kunes
authors.affiliation: Department of Clinical Microbiology, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic. vladimir.buchta@fnhk.cz.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Buchta
authors.affiliation: Department of Clinical Microbiology, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic. marcela.vejsova@fnhk.cz.
authors.forename: Marcela
authors.initials: M
authors.lastname: Vejsova
authors.affiliation: Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic. veronika.opletalova@faf.cuni.cz.
authors.forename: Veronika
authors.initials: V
authors.lastname: Opletalova
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002522:Chlorocebus aethiops; D005658:Fungi / Q000145:classification / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D066244:Proton Magnetic Resonance Spectroscopy; D011719:Pyrazines / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D014709:Vero Cells
chemical_list: D000935:Antifungal Agents; D000995:Antitubercular Agents; D047188:Chalcones; D011719:Pyrazines