Saito H, Hirata T, Kasai M, Fujimoto K, Ashizawa T, Morimoto M, Sato A
Tokyo Research Laboratories, Kyowa Hakko Kogyo Company, Ltd., Japan.
J Med Chem. 1991 Jul;34(7):1959-66. doi: 10.1021/jm00111a006.
Varieties of thioalkyl-containing quinone and hydroquinone analogues of quinocarcin (1a) were prepared effectively, by addition of mercaptan to 3a-c, which were derived from 1a via DX-52-1 (1b). Antitumor activities of these analogues were preliminarily evaluated by growth inhibition of HeLa S3 cells (in vitro) and increased life span of P388 implanted mice (in vivo). Bis(alkylthio)quinones 4a-d and 5a-d, and corresponding hydroquinones 9b-d exhibited high activities both in vitro and in vivo. They were superior to 1a especially in single administration. Selected compounds 4a, 4d, 5a, 5d, and 9b were subjected to further evaluation, and bis(methylthio)quinone 5a was revealed to possess broad-spectrum activity toward human xenographted carcinomas MX-1, Co-3, St-4, and LC-06.
通过将硫醇添加到经由 DX - 52 - 1（1b）从醌癌菌素（1a）衍生而来的 3a - c 中，有效地制备了多种含硫代烷基的醌癌菌素（1a）的醌和对苯二酚类似物。这些类似物的抗肿瘤活性通过 HeLa S3 细胞的生长抑制（体外）和植入 P388 小鼠的寿命延长（体内）进行了初步评估。双（烷基硫代）醌 4a - d 和 5a - d 以及相应的对苯二酚 9b - d 在体外和体内均表现出高活性。它们尤其在单次给药时优于 1a。对选定的化合物 4a、4d、5a、5d 和 9b 进行了进一步评估，结果表明双（甲硫基）醌 5a 对人异种移植癌 MX - 1、Co - 3、St - 4 和 LC - 06 具有广谱活性。
