Dihydropyrazine derivatives as a new type of DNA strand breaking agent

Article abstract of DOI:10.1248/bpb.19.1261

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 plasmid 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 solution. 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.

Full text of DOI:10.1248/bpb.19.1261

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