a Faculty of Chemistry , Alexandru Ioan Cuza University of Iasi , Iasi , Romania.
b CERNESIM Research Centre, Alexandru Ioan Cuza University of Iasi , Iasi , Romania.
J Enzyme Inhib Med Chem. 2019 Dec;34(1):230-243. doi: 10.1080/14756366.2018.1550085.
Two new series of heterocyclic derivatives with potential anticancer activity, in which a pyrrolo[1,2-b]pyridazine or a pyrrolo[2,1-a]phthalazine moiety was introduced in place of the 3'-hydroxy-4'-methoxyphenyl ring of phenstatin have been synthesised and their structure-activity relationship (SAR) was studied. Fourteen of the new compounds were evaluated for their in vitro cytotoxic activity by National Cancer Institute (NCI) against 60 human tumour cell lines panel. The best five compounds in terms of in vitro growth inhibition were screened in the second stage five dose-response studies, three of them showing a very good antiproliferative activity with GI<100 nM on several cell lines including colon, ovarian, renal, prostate, brain and breast cancer, melanoma and leukemia. Docking experiments on the biologically active compounds showed a good compatibility with the colchicine binding site of tubulin.
已经合成了两个具有潜在抗癌活性的杂环衍生物新系列，其中吡咯并[1,2-b]哒嗪或吡咯并[2,1-a]酞嗪部分取代苯并噻唑中 3'-羟基-4'-甲氧基苯基环，研究了它们的结构-活性关系（SAR）。根据国家癌症研究所（NCI）对 60 个人类肿瘤细胞系的评估，对 14 种新化合物进行了体外细胞毒性活性评估。在第二阶段的五项剂量反应研究中，筛选出五个在体外生长抑制方面表现最佳的化合物，其中三个化合物对包括结肠癌、卵巢癌、肾癌、前列腺癌、脑癌和乳腺癌、黑色素瘤和白血病在内的几种细胞系表现出非常好的抗增殖活性，GI<100nM。对生物活性化合物的对接实验表明，与微管蛋白的秋水仙碱结合位点具有良好的兼容性。
