Toxicities of dicyanobenzofurazans with formation of superoxide in Escherichia coli.
The toxicities of some benzofurazans (BZs), benzofurazan (1), 4,7-dimethylbenzofurazan (2), 4,7-dibromobenzofurazan (3), 4-bromo-6-cyanobenzofurazan (4), 4,7-dicyanobenzofurazan (5) and 4,5-dicyanobenzofurazan (6), were examined on Escherichia coli. Compound 5 at 4 microM and compound 6 at 7 microM completely inhibited the growth of E. coli in a simple nutritionally restricted medium (GM medium). These compounds were more toxic in GM medium than in a nutritionally rich medium (YE medium), which contained yeast extract as an additive in GM medium. Compound 4 also inhibited the growth of E. coli at 300 microM in GM medium. The toxicities of BZs were in the order of 1 approximately 2 approximately 3 less than 4 approximately 5 approximately 6. Compounds 4, 5 and 6 induced manganese-superoxide dismutase (Mn-SOD) and catalase activities of E. coli in YE medium. The induced SOD and catalase provide a defense against the potential cytotoxicities of O2- and H2O2. The rate of dioxygen uptake in cyanide-resistant respiration of E. coli was dependent on the concentration of 5, and was correlated with the induction of SOD and catalase. The reduction potentials of BZs followed the order of 1 approximately 2 less than 3 less than 4 less than 5 approximately 6. Compounds 5 and 6, which had redox potentials higher than those of the other BZs, are thought to be more readily reduced in the living system.(ABSTRACT TRUNCATED AT 250 WORDS)
Takabatake
T
T
Department of Pharmacy, College of Science & Technology, Nihon University, Tokyo, Japan.
Hasegawa
M
M
Nagano
T
T
Hirobe
M
M
D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000633:toxicity; D002374:Catalase / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009570:Nitriles / Q000138:chemical synthesis / Q000633:toxicity; D010101:Oxygen Consumption / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D001583:Benzoxazoles; D009570:Nitriles; D013481:Superoxides; D002374:Catalase; D013482:Superoxide Dismutase