Inomata M, Fukuoka F, Hoshi A, Kuretani K, Saneyoshi M
J Pharmacobiodyn. 1981 Jan;4(1):58-64. doi: 10.1248/bpb1978.4.58.
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 ED50) and higher toxicity to host (lower LD50) than parent compounds, but ratios of increase in activity and toxicity were different with each other. The compounds with higher chemotherapeutic index (LD50/ED50) than parent compounds were alpha-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 alpha-naphthyryl (28) disulfides in a series of 6-TG (14) derivatives. These 6-TG derivatives were promising for antitumor agents.
通过肠胃外给药，在小鼠腹水肉瘤-180系统（总红细胞压积法）中检测了新合成的6-巯基嘌呤（6-MP）和6-硫鸟嘌呤（6-TG）二硫化物衍生物对宿主的抗肿瘤活性和毒性。所测试的化合物为6-烷基二硫化物（烷基的碳原子数：2、3、4、5、6、7、8、10和14）、6-支链烷基二硫化物（异丙基、仲丁基和叔丁基）以及6-芳烷基二硫化物（萘基）。6-MP和6-TG的大多数二硫化物衍生物显示出比母体化合物更高的抗肿瘤活性（更低的半数有效剂量ED50）和对宿主更高的毒性（更低的半数致死剂量LD50），但活性和毒性的增加比例彼此不同。化疗指数（LD50/ED50）高于母体化合物的化合物有：在一系列6-MP（化疗指数为7.5）衍生物中的α-萘基（化疗指数为8.7）二硫化物；以及在一系列6-TG（化疗指数为14）衍生物中的仲丁基（化疗指数为27）、叔丁基（化疗指数为24）、辛基（化疗指数为23）、癸基（化疗指数为26）和α-萘基（化疗指数为28）二硫化物。这些6-TG衍生物有望成为抗肿瘤药物。
