title: New potentially active pyrazinamide derivatives synthesized under microwave conditions.
abstract: A series of 18 N-alkyl substituted 3-aminopyrazine-2-carboxamides was prepared in this work according to previously experimentally set and proven conditions using microwave assisted synthesis methodology. This approach for the aminodehalogenation reaction was chosen due to higher yields and shorter reaction times compared to organic reactions with conventional heating. Antimycobacterial, antibacterial, antifungal and photosynthetic electron transport (PET) inhibiting in vitro activities of these compounds were investigated. Experiments for the determination of lipophilicity were also performed. Only a small number of substances with alicyclic side chain showed activity against fungi which was the same or higher than standards and the biological efficacy of the compounds increased with rising lipophilicity. Nine pyrazinamide derivatives also inhibited PET in spinach chloroplasts and the IC50 values of these compounds varied in the range from 14.3 to 1590.0 μmol/L. The inhibitory activity was connected not only with the lipophilicity, but also with the presence of secondary amine fragment bounded to the pyrazine ring. Structure-activity relationships are discussed as well.
authors.affiliation: Department of Medicinal Chemistry and Drug Analysis, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. jando6aa@faf.cuni.cz.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Jandourek
authors.affiliation: Department of Medicinal Chemistry and Drug Analysis, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. dolezalm@faf.cuni.cz.
authors.forename: Martin
authors.initials: M
authors.lastname: Dolezal
authors.affiliation: Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. kunes@faf.cuni.cz.
authors.forename: Jiri
authors.initials: J
authors.lastname: Kunes
authors.affiliation: Department of Biophysics and Physical Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. kubicek@faf.cuni.cz.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kubicek
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. pavla.paterova@fnhk.cz.
authors.forename: Pavla
authors.initials: P
authors.lastname: Paterova
authors.affiliation: Department of Environmental Ecology, Faculty of Natural Sciences, Comenius University, Mlynska Dolina CH-2, Bratislava 842 15, Slovakia. matus.pesko@gmail.com.
authors.forename: Matus
authors.initials: M
authors.lastname: Pesko
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. vladimir.buchta@fnhk.cz.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Buchta
authors.affiliation: Institute of Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska Dolina CH-2, Bratislava 842 15, Slovakia. kata.kralova@gmail.com.
authors.forename: Katarina
authors.initials: K
authors.lastname: Kralova
authors.affiliation: Department of Medicinal Chemistry and Drug Analysis, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. zitkj3aa@faf.cuni.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Zitko
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002736:Chloroplasts / Q000187:drug effects / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D006540:Herbicides / Q000138:chemical synthesis* / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D008872:Microwaves; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010788:Photosynthesis / Q000187:drug effects; D011718:Pyrazinamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D018724:Spinacia oleracea / Q000187:drug effects / Q000378:metabolism; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D000995:Antitubercular Agents; D006540:Herbicides; D011718:Pyrazinamide