Effects of phenyl derivatives of dihydropyrazines with ability to generate radical species on Escherichia coli.
Phenyl-substituted dihydropyrazines (Ph-DHPs) are derivatives of 2,3-dihydro-5,6-dimethylpyrazine (Me-DHP). Upon the addition of Cu(2+), Me-DHP inhibits the growth of Escherichia coli by generating hydroxyl and carbon-centered radicals that cause DNA strand breakage. Here, we investigated the toxic effect of Ph-DHPs in several DNA repair-deficient or detoxifying enzyme-deficient mutant strains. Ph-DHPs caused cytotoxic and genotoxic damage, but, in a sodA sodB strain, the effects in the presence or absence of Cu(2+) were different than those of Me-DHP. Our results suggest that the action of the generated superoxide anion in the interior side of the cell is remarkable.
Takeda
Osamu
O
Department of Public Health, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
Takechi
Shinji
S
Ito
Shigeru
S
Omori
Hisamitsu
H
Katoh
Takahiko
T
Yamaguchi
Tadatoshi
T
D000622:Aminolevulinic Acid / Q000378:metabolism; D003300:Copper / Q000494:pharmacology; D004247:DNA / Q000187:drug effects / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects; D004578:Electron Spin Resonance Spectroscopy; D048168:Escherichia coli K12 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology; D009154:Mutation; D010647:Phenyl Ethers / Q000737:chemistry / Q000378:metabolism; D011719:Pyrazines / Q000737:chemistry / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000378:metabolism