College of Pharmacy, Duksung Women's University, Seoul, 132-714, Korea.
Arch Pharm Res. 2015;38(5):791-800. doi: 10.1007/s12272-014-0416-3. Epub 2014 Jun 14.
A new series of 6-allylthio-3-aralkylthio-4,5-dimethylpyridazines 5a-5k and 1-allylthio-4-alkylthio-5,6,7,8-tetrahydrophthalazine 6a-6j was synthesized from maleic anhydride derivatives for development of new anticancer agents. The process involves the formation of pyridazine and phthalazine rings, dichlorination, allylthiolation, and aralkylthiolation. These new compounds showed antiproliferative activities against breast cancer (MCF-7) and hepatocarcinoma (Hep3B) cells in CCK-8 assays, and could be promising candidates for chemotherapy of carcinomas. Among 21 synthesized compounds, five compounds (5a, 5b, 6b, 6d, and 6f) showed higher potency than 5-FU for inhibiting the growth of cell line. The results indicated that compound 6f had the highest activity towards MCF-7 and Hep3B cells. These results suggest the potential anticancer activity of compounds 5a, 5b, 6b, 6d, and 6f.
从马来酸酐衍生物出发，合成了一系列新的 6-烯丙基硫基-3-芳烷基硫基-4,5-二甲基哒嗪 5a-5k 和 1-烯丙基硫基-4-烷基硫基-5,6,7,8-四氢邻苯二甲嗪 6a-6j，用于开发新的抗癌药物。该过程涉及哒嗪和邻苯二甲嗪环的形成、二氯化、烯丙基硫代和芳基硫代。这些新化合物在 CCK-8 测定中表现出对乳腺癌（MCF-7）和肝癌（Hep3B）细胞的增殖抑制活性，可能是癌症化疗的有前途的候选药物。在所合成的 21 种化合物中，有 5 种化合物（5a、5b、6b、6d 和 6f）对细胞系的生长抑制作用强于 5-FU。结果表明，化合物 6f 对 MCF-7 和 Hep3B 细胞的活性最高。这些结果表明化合物 5a、5b、6b、6d 和 6f 具有潜在的抗癌活性。
