Synthesis and antimycobacterial evaluation of substituted pyrazinecarboxamides.
Unsubstituted, halogenated and/or alkylated pyrazine-2-carboxylic acid amides connected via -CONH- bridge with substituted anilines were synthesized using currently known synthetic pathways. The synthetic approach, analytical, spectroscopic, lipophilicity and biological data of 20 newly synthesized compounds are presented. Structure-activity relationships among the chemical structures, the antimycobacterial, antifungal, photosynthesis inhibiting and antialgal activity of the evaluated substituted N-phenylpyrazine-2-carboxamides are discussed. 5-tert-Butyl-6-chloro-N-(3-trifluoromethylphenyl)pyrazine-2-carboxamide (19) has shown the highest activity against Mycobacterium tuberculosis H(37)Rv (MIC=3.13 microg/mL). The highest antifungal effect against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for N-(3-trifluoromethylphenyl)pyrazine-2-carboxamide (14, MIC=62.5 micromol/mL). The highest reduction of chlorophyll content in Chlorella vulgaris was found for pyrazine-2-carboxylic acid (3-trifluoromethylphenyl)amide (9, IC(50)=12.1 micromol/L).
Dolezal
Martin
M
Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic. dolezalm@faf.cuni.cz
Cmedlova
Pavlina
P
Palek
Lukas
L
Vinsova
Jarmila
J
Kunes
Jiri
J
Buchta
Vladimir
V
Jampilek
Josef
J
Kralova
Katarina
K
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D048408:Chlorella vulgaris / Q000187:drug effects / Q000378:metabolism; D002522:Chlorocebus aethiops; D002734:Chlorophyll / Q000378:metabolism; D002736:Chloroplasts / Q000187:drug effects / Q000378:metabolism; D006540:Herbicides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018724:Spinacia oleracea / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D014709:Vero Cells
D000577:Amides; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D006540:Herbicides; D011719:Pyrazines; D002734:Chlorophyll