Generation of radical species from dihydropyrazines having DNA strand-breakage activity and other characteristics.
The various biological activity of dihydropyrazines(DHPs)due to the radical generation potency has been described in previous papers. Detailed data about radical species generating be mentioned here. The electron spin resonance (ESR) spin-trapping technique revealed that DHPs generate free radical species such as ·OH, ·OOH, ·CHR(2) and ·CR(3). Oxygen radicals and two carbon-centered radicals were detected as adducts of the spin traps DMPO and DBNBS, respectively. All the 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)- and 3,5-dibromo-4-nitrosobenzenesulfonate (DBNBS)-adducts of compounds DHP-1-8 exhibited approximately the same signal patterns, with various levels of intensity depending on the substituent of the dihydropyrazine ring. The ESR signal intensity of DHPs also increased remarkably upon addition of Cu(2+), resulting that the effects of DHPs were enhanced.
Pharmaceutical Sciences, Sojo University, Kumamoto 860–0082, Japan. tadayama@ph.sojo-u.ac.jp
Tadatoshi
T
Yamaguchi
Shigenobu
S
Matsumoto
Toshiki
T
Masumizu
Shinji
S
Takechi
Takumi
T
Ishida
Keizo
K
Takeshita
Hisao
H
Kansui
Takehisa
T
Kunieda
D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism*; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry*
D005609:Free Radicals; D011719:Pyrazines; D004247:DNA