Synthesis, antimycobacterial, antifungal and photosynthesis-inhibiting activity of chlorinated N-phenylpyrazine-2-carboxamides.
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.
Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove, 500 05, Czech Republic. martin.dolezal@faf.cuni.cz
Martin
M
Dolezal
Jan
J
Zitko
Zdenek
Z
Osicka
Jiri
J
Kunes
Marcela
M
Vejsova
Vladimir
V
Buchta
Jiri
J
Dohnal
Josef
J
Jampilek
Katarina
K
Kralova
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002736:Chloroplasts / Q000378:metabolism*; D006843:Hydrocarbons, Chlorinated / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000254:growth & development*; D010788:Photosynthesis / Q000187:drug effects*; D011718:Pyrazinamide / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018724:Spinacia oleracea / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014249:Trichophyton / Q000254:growth & development*
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D006843:Hydrocarbons, Chlorinated; D011718:Pyrazinamide