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Molecules 2010, 15(12), 8567-8581; doi:10.3390/molecules15128567
Article

Synthesis, Antimycobacterial, Antifungal and Photosynthesis-Inhibiting Activity of Chlorinated N-phenylpyrazine-2-carboxamides

1,* , 1
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1 Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove, 500 05, Czech Republic 2 Bioveta a.s., Komenskeho 212, 683 23 Ivanovice na Hane, Czech Republic 3 Department of Clinical Microbiology, Faculty of Medicine and University Hospital, Charles University in Prague, Sokolska 581, Hradec Kralove, 500 05, Czech Republic 4 Zentiva k.s., U Kabelovny 130, 102 37 Prague 10, Czech Republic 5 Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 61242 Brno, Czech Republic 6 Institute of Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska Dolina CH-2, 842 15 Bratislava, Slovak Republic Preliminary results were presented at the Fourteenth Electronic Conference on Synthetic Organic Chemistry (ECSOC-14, http://www.sciforum.net/presentation/380), November 1-30, 2010.
* Author to whom correspondence should be addressed.
Received: 15 November 2010 / Revised: 22 November 2010 / Accepted: 25 November 2010 / Published: 26 November 2010
(This article belongs to the Special Issue ECSOC-12)
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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 pyrazinecarboxamides; lipophilicity; in vitro antimycobacterial activity; in vitro antifungal activity; spinach chloroplasts; PET inhibition; structure–activity relationships
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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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.

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