Abstract: A series of sixteen pyrazinamide analogues with the -CONH- linker connecting the pyrazine and benzene rings was synthesized by the condensation of chlorides of substituted pyrazinecarboxylic acids with ring-substituted (chlorine) anilines. The prepared compounds were characterized and evaluated for their antimycobacterial and antifungal activity, and for their ability to inhibit photosynthetic electron transport (PET). 6-Chloro-N-(4-chlorophenyl)pyrazine-2-carboxamide manifested the highest activity against Mycobacterium tuberculosis strain H37Rv (65% inhibition at 6.25 μg/mL). The highest antifungal effect against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for 6-chloro-5-tert-butyl-N-(3,4-dichlorophenyl)pyrazine-2-carboxamide (MIC = 62.5 μmol/L). 6-Chloro-5-tert-butyl-N-(4-chlorophenyl)pyrazine-2-carboxamide showed the highest PET inhibition in spinach chloroplasts (Spinacia oleracea L.) chloroplasts (IC50 = 43.0 μmol/L). For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds as well as their structure-activity relationships are discussed.
Keywords: pyrazinecarboxamides; lipophilicity; in vitro antimycobacterial activity; in vitro antifungal activity; spinach chloroplasts; PET inhibition; structure–activity relationships
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Dolezal, M.; Zitko, J.; Osicka, Z.; Kunes, J.; Vejsova, M.; Buchta, V.; Dohnal, J.; Jampilek, J.; Kralova, K. Synthesis, Antimycobacterial, Antifungal and Photosynthesis-Inhibiting Activity of Chlorinated N-phenylpyrazine-2-carboxamides †. Molecules 2010, 15, 8567-8581.
Dolezal M, Zitko J, Osicka Z, Kunes J, Vejsova M, Buchta V, Dohnal J, Jampilek J, Kralova K. Synthesis, Antimycobacterial, Antifungal and Photosynthesis-Inhibiting Activity of Chlorinated N-phenylpyrazine-2-carboxamides †. Molecules. 2010; 15(12):8567-8581.
Dolezal, Martin; Zitko, Jan; Osicka, Zdenek; Kunes, Jiri; Vejsova, Marcela; Buchta, Vladimir; Dohnal, Jiri; Jampilek, Josef; Kralova, Katarina. 2010. "Synthesis, Antimycobacterial, Antifungal and Photosynthesis-Inhibiting Activity of Chlorinated N-phenylpyrazine-2-carboxamides †." Molecules 15, no. 12: 8567-8581.