Gabr Moustafa T, El-Gohary Nadia S, El-Bendary Eman R, El-Kerdawy Mohamed M, Ni Nanting
Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt; Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.
Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Eur J Med Chem. 2017 Mar 10;128:36-44. doi: 10.1016/j.ejmech.2017.01.030. Epub 2017 Jan 23.
A new series of isatin-β-thiocarbohydrazones was synthesized based on the pharmacophoric features of triapine required for metal chelation. Our strategy involved the modifications of triapine basic skeleton by replacing pyridinyl moiety with isatin which retains the tridentate feature of triapine needed for metal chelation. The new compounds were esteemed for their antitumor efficacy against cervical cancer (Hela) and kidney fibroblast cancer (COS-7) cell lines. Compounds 4c, 4d, 5c and 5e exhibited remarkable efficacy against Hela cell line. In addition, compounds 4c, 4k, 4e, 5c and 5e displayed an outstanding efficacy against COS-7 cell line. Compounds 4c, 4k, 4e, 5c and 5e were examined for their in vivo antitumor efficacy against Ehrlich ascites carcinoma (EAC) in mice. Pharmacophore mapping was performed to study the structural features of the synthesized compounds compared to triapine and to identify the essential moieties required for potent and selective antitumor activity.
基于曲拉匹明进行金属螯合所需的药效团特征，合成了一系列新的异吲哚酮-β-硫代碳腙。我们的策略是通过用异吲哚酮取代吡啶基部分来修饰曲拉匹明的基本骨架，而异吲哚酮保留了曲拉匹明进行金属螯合所需的三齿特征。这些新化合物因其对子宫颈癌（Hela）和肾成纤维细胞瘤（COS-7）细胞系的抗肿瘤功效而受到重视。化合物4c、4d、5c和5e对Hela细胞系表现出显著的功效。此外，化合物4c、4k、4e、5c和5e对COS-7细胞系显示出出色的功效。研究了化合物4c、4k、4e、5c和5e对小鼠艾氏腹水癌（EAC）的体内抗肿瘤功效。进行了药效团映射，以研究合成化合物与曲拉匹明相比的结构特征，并确定有效和选择性抗肿瘤活性所需的必需部分。
