al-Obaid A M, el-Subbagh H I, Khodair A I, Elmazar M M
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Anticancer Drugs. 1996 Nov;7(8):873-80. doi: 10.1097/00001813-199611000-00009.
Certain series of 2-thiohydantoin derivatives, carrying various substituents at position 5 such as 5-bromo-2-thienylmethylene, 5-(2-carboxyphenylthio)-2-thienylmethylene and 2-methylene-4H-thieno[2,3-b][1]benzothiopyran-4-one, were evaluated for their antitumor activity. Compound 5-(5-bromo-2-thienylmethylene)-3-morpholinomethyl-2-(2,3,4,6 -tetra-O-acetyl -beta-D-glucopyranosylthio)hydantoin proved to possess a broad spectrum antitumor activity against a wide range of different human cell lines of nine tumor subpanels causing both cytostatic and cytotoxic effects, resulting in full panel median growth inhibition (GI50) and total growth inhibition (TGI), with a median lethal concentration (LC50) at 15.1, 41.7 and 83.2 microM, respectively. On the other hand, compound 5-(5-bromo-2-thienylmethylene)-2-thiohydantoin and compound 5-(5-bromo-2-thienylmethylene)-3-phenyl-2- (2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl-thio)hydantoin showed potential selectivity against leukemia cell lines. Further derivatization of these compounds, deduced from the obtained tentative structure-activity relationships, may lead to more potent agents.
对某些在5位带有各种取代基的2-硫代乙内酰脲衍生物系列进行了抗肿瘤活性评估，这些取代基如5-溴-2-噻吩基亚甲基、5-(2-羧基苯硫基)-2-噻吩基亚甲基和2-亚甲基-4H-噻吩并[2,3-b][1]苯并噻喃-4-酮。化合物5-(5-溴-2-噻吩基亚甲基)-3-吗啉甲基-2-(2,3,4,6-四-O-乙酰基-β-D-吡喃葡萄糖硫基)乙内酰脲被证明对九种肿瘤亚组的多种不同人类细胞系具有广谱抗肿瘤活性，可产生细胞生长抑制和细胞毒性作用，导致全组中位生长抑制(GI50)和完全生长抑制(TGI)，中位致死浓度(LC50)分别为15.1、41.7和83.2微摩尔。另一方面，化合物5-(5-溴-2-噻吩基亚甲基)-2-硫代乙内酰脲和化合物5-(5-溴-2-噻吩基亚甲基)-3-苯基-2-(2,3,4,6-四-O-乙酰基-β-D-吡喃半乳糖硫基)乙内酰脲对白血病细胞系表现出潜在的选择性。根据所获得的初步构效关系对这些化合物进行进一步衍生化，可能会产生更有效的药物。
