Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, 69 Pekarska, Lviv 79010, Ukraine; Department of Organic Chemistry and Pharmacy, Lesya Ukrainka Eastern European National University, Volya Avenue 13, 43025 Lutsk, Ukraine.
Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, 69 Pekarska, Lviv 79010, Ukraine.
Bioorg Chem. 2019 May;86:126-136. doi: 10.1016/j.bioorg.2019.01.045. Epub 2019 Jan 22.
A series of novel 2-(5-aminomethylene-4-oxo-2-thioxothiazolidin-3-yl)-3-phenylpropionic acid ethyl esters has been synthesized. Target compounds were evaluated for their trypanocidal activity towards Trypanosoma brucei brucei and Trypanosoma brucei gambiense. Several hit-compounds (8, 10, 12) inhibited growth of the parasites at sub-micromolar concentrations (IC 0.027-1.936 µM) and showed significant selectivity indices (SI = 108-1396.2) being non-toxic towards the human primary fibroblasts. The screening of anticancer activity in vitro within NCI DTP protocol allowed to identify active 2-(5-{[5-(2,4-dichlorobenzyl)-thiazol-2-ylamino]-methylene}-4-oxo-2-thioxothiazolidin-3-yl)-3-phenylpropionic acid ethyl ester 14 that demonstrated inhibition against all 59 human tumor cell lines with the average GI value of 2.57 μM. It was established that the activity type (antitrypanosomal or anticancer) as well as its level depends on the character of enamine fragment in the C5 position of thiazolidinone core.
已经合成了一系列新型 2-(5-亚氨基甲叉-4-氧代-2-噻唑啉-3-基)-3-苯基丙酸乙酯。目标化合物被评估了它们对布氏锥虫和布氏冈比亚锥虫的杀锥虫活性。一些命中化合物（8、10、12）在亚微米浓度（IC 0.027-1.936 µM）下抑制寄生虫生长，并显示出显著的选择性指数（SI=108-1396.2），对人原代成纤维细胞没有毒性。在 NCI DTP 方案中进行的体外抗癌活性筛选，鉴定出活性 2-(5-[[5-(2,4-二氯苄基)-噻唑-2-基氨基]-亚甲基]-4-氧代-2-噻唑啉-3-基）-3-苯基丙酸乙酯 14，对所有 59 个人类肿瘤细胞系均表现出抑制作用，平均 GI 值为 2.57 μM。已经确定，活性类型（抗锥虫或抗癌）及其水平取决于噻唑烷酮核心 C5 位置烯胺片段的性质。
