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Identification of a class of sulfonamides highly active against dihydropteroate synthase from Toxoplasma gondii, Pneumocystis carinii, and Mycobacterium avium


, : Identification of a class of sulfonamides highly active against dihydropteroate synthase from Toxoplasma gondii, Pneumocystis carinii, and Mycobacterium avium. Antimicrobial Agents & Chemotherapy 40(3): 727-733

Sulfanilanilides with 3',5'-halogen substitutions had K-i values 6- to 57-fold lower than the K-i of sulfamethoxazole when tested against dihydropteroate synthase from Toxoplasma gondii. The compounds acted as competitive inhibitors. These compounds were also active against dihydropteroate synthase from Pneumocystis carinii, Mycobacterium avium, and Escherichia coli but were not significantly more active than sulfamethoxazole. The compounds were significantly more active in culture than were standard agents. Against T. gondii in culture, 50% inhibitory concentrations were 7- to 30-fold lower than that of sulfadiazine; against P. carinii in culture, a concentration of 100 mu-M caused 33 to 95% inhibition of growth, compared with 9% inhibition with 100 mu-M sulfamethoxazole.

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