Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Toxicities of Dicyanobenzofurazans with Formation of Superoxide in Escherichia coli
Tohru TAKABATAKEMinoru HASEGAWATetsuo NAGANOMasaaki HIROBE
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JOURNAL FREE ACCESS

1990 Volume 38 Issue 1 Pages 128-132

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Abstract

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 μM and compound 6 at 7 μM 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 μM in GM medium. The toxicities of BZs were in the order of 1&ap;2&ap;3<4«5&ap;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&ap;2<3<4<5&ap;6. Compounds 5 and 6, which had redox potentials higher than those of the order BZs, are thought to be more readily reduced in the living system. The present results suggest that the toxicities of compounds 5 and 6 to E. coli are due to their reduction within the E. coli cell and their reoxidization by molecular dioxygen to form superoxide (O20-) and hydrogen peroxide (H2O2). Compound 4 was also suggested to damage E. coli through the same mechanism. though it was less toxic.

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© The Pharmaceutical Society of Japan
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