title: Synthesis and Biological Evaluation of N-Alkyl-3-(alkylamino)-pyrazine-2-carboxamides.
abstract: A series of N-alkyl-3-(alkylamino)pyrazine-2-carboxamides and their N-alkyl-3-chloropyrazine-2-carboxamide precursors were prepared. All compounds were characterized by analytical methods and tested for antimicrobial and antiviral activity. The antimycobacterial MIC values against Mycobacterium tuberculosis H37Rv of the most effective compounds, 3-(hexylamino)-, 3-(heptylamino)- and 3-(octylamino)-N-methyl-pyrazine-2-carboxamides 14‒16, was 25 μg/mL. The compounds inhibited photosystem 2 photosynthetic electron transport (PET) in spinach chloroplasts. This activity was strongly connected with the lipophilicity of the compounds. For effective PET inhibition longer alkyl chains in the 3-(alkylamino) substituent in the N-alkyl-3-(alkylamino)pyrazine-2-carboxamide molecule were more favourable than two shorter alkyl chains.
authors.affiliation: Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. semelkol@faf.cuni.cz.
authors.forename: Lucia
authors.initials: L
authors.lastname: Semelkova
authors.affiliation: Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. konecna@faf.cuni.cz.
authors.forename: Klara
authors.initials: K
authors.lastname: Konecna
authors.affiliation: 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: 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: 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: Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. novakoval@faf.cuni.cz.
authors.forename: Lucie
authors.initials: L
authors.lastname: Novakova
authors.affiliation: Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. marej1aa@faf.cuni.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Marek
authors.affiliation: Laboratory of Virology and Chemotherapy, Rega Institute KU Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium. lieve.naesens@rega.kuleuven.be.
authors.forename: Lieve
authors.initials: L
authors.lastname: Naesens
authors.affiliation: Department of Environmental Ecology, Faculty of Natural Sciences, Comenius University, Mlynska Dolina CH-2, Bratislava 84215, Slovakia. matus.pesko@gmail.com.
authors.forename: Matus
authors.initials: M
authors.lastname: Pesko
authors.affiliation: Institute of Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska Dolina CH-2, Bratislava 84215, Slovakia. kralova@fns.uniba.sk.
authors.forename: Katarina
authors.initials: K
authors.lastname: Kralova
authors.affiliation: 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: Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. jan.zitko@faf.cuni.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Zitko
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002736:Chloroplasts / Q000378:metabolism*; D004579:Electron Transport / Q000187:drug effects*; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000378:metabolism; D011718:Pyrazinamide / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011719:Pyrazines / Q000138:chemical synthesis / Q000494:pharmacology*; D018724:Spinacia oleracea / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D011719:Pyrazines; D011718:Pyrazinamide; D064429:Fatty Acid Synthases; C413881:fatty acid synthase I, mycobacteria
keywords: alkylation; aminodehalogenation; antimycobacterial activity; inhibition of photosynthetic electron transport; pyrazinamide; pyrazine; structure-activity relationships