Dihydropyrazine Derivatives as a New Type of DNA Strand Breaking Agent

抄録

The DNA strand-breaking activity of some dihydropyrazine derivatives, 2, 3-dihydro-5, 6-dimethylpyrazine (3), 2, 3-dihydro-2, 5, 6-trimethylpyrazine (4), 2, 3-dihydro-2, 2, 5, 6-tetramethylpyrazine (5), trans-2, 3-dimethyl-5, 6, 7, 8, 9, 10-hexahydroquinoxaline (6), its cis-compound (7) and the mixture of 6 and 7 (8) was tested by agarose gel electrophoresis using plasmide pBR322 ccc-DNA as a substrate. The order of DNA strand-breaking activity in the presence of Cu²⁺ was (7)>(8)≥(5)>(2)>(6)>(4)≥(1)≥(3). 2, 5-Bis(D-arabino-tetrahydroxybutyl)-2, 5-dihydropyrazine (1) and 2, 5-dihydro-3, 6-dimethylpyrazine (2) have already been described in terms of DNA breaking activity in a previous paper.The activity was suggested to be due to the dihydropyrazine skeleton, in addition to active oxygen radicals formed in an aqueous solutoin. The introduction of a methyl group to the dihydropyrazine skeleton enhanced the activities of dihydropyrazine derivatives. The possible chemical basis for DNA strand breakage by dihydropyrazine derivatives, especially in the presence of Cu²⁺, was discussed.