STRUCTURE-ANTITUMOR ACTIVITY RELATIONSHIP OF PURIN-6-YL ALKYL DISULFIDES

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Antitumor activity and toxicity to host of newly synthesized disulfide derivatives of 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) were examined in murine ascites sarcoma-180 system (total packed cell volume method) by parenteral administration. The compounds tested were 6-alkyl disulfides (carbon number of alkyl group : 2,3,4,5,6,7,8,10,and 14), 6-branched-alkyl disulfides (iso-propyl, sec-butyl, and tert-butyl), and 6-aralkyl disulfide (naphthyryl). Most disulfide derivatives of 6-MP and 6-TG showed higher antitumor activity (lower ED_<50>) and higher toxicity to host (lower LD_<50>) than parent compounds, but ratios of increase in activity and toxicity were different with each other. The compounds with higher chemotherapeutic index (LD_<50>/ED_<50>) than parent compounds were α-naphthyryl (8.7) disulfide in a series of 6-MP (7.5) derivatives ; and sec-butyl (27), tert-butyl (24), octyl (23), decyl (26), and α-naphthyryl (28) disulfides in a series of 6-TG (14) derivatives These 6-TG derivatives were promising for antitumor agents.
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