新規抗癌剤Bis(haloalkyl)piperidine誘導体のDeoxyribonucleic Acidにおよぼす影響

概要

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In order to elucidate the mechanism of action of new antitumor agents like bis-(haloalkyl) piperidine (CAP) derivatives, the influence of three typical derivatives, 1-(β-chloroethyl)-2-chloromethylpiperidine hydrobromide (CAP-1), 1-(γ-chloropropyl)-2-chloromethylpiperidine hydrobromide (CAP-2), and 2,6-bis (iodomethyl) piperidine hydrochloride (CAP-12), on the synthesis of nucleic acid and protein was examined by use of rat ascites hepatoma AH-13 cells, and the binding mode of these compounds to deoxyribonucleic acid (DNA) was also studied by the ultracentrifugation of purified phage P 22 DNA in alkaline sucrose gradient. The incorporation of ^3H-thymidine was decreased but those of ^3H-uridine and ^3H-leucine increased by all compounds, and CAP-1 acted most significantly. On the other hand, the contents of nucleic acid and protein per cell all increased to approximately 160% of the control value in 24 hr. Furthermore, the DNA treated with CAP-1 was shifted to higher density position of alkaline sucrose than the untreated DNA, while in the case of CAP-2 and CAP-12,the DNA was scarcely shifted. From these findings, it was deduced that the antitumor activity of these compounds results from inhibition of DNA synthesis and production of unbalanced cell growth after formation of the interstrand crosslinkage of DNA by CAP-1 and some other alkylation to DNA by CAP-2 or CAP-12.
社団法人日本薬学会の論文
1980-08-25