Abstract

A series of new substituted triazolo[4,5-d]pyrimidine derivatives linked to thienopyrimidine ring system were prepared as a hybrid heterocyclic systems, as possible nucleobases analogs, starting from the key carboxamide derivative 2 and its azide precursor via heterocyclization reactions and their structures were characterized. Glycosylation of the prepared triazolopyrimidine derivatives was performed and afforded, regioselctively, the corresponding thienopyrimidine-triazolopyrimidine hybrid N¹-glycosides and their thioglycoside analogues in good yields. The synthesized glycosyl heterocycles were studied for their cytotoxic activity against HepG-2 and MCF-7 human cancer cells and significant results were obtained. Compounds 7a, 8 b, 9 b, 9a and 7 b demonstrated promising activities comparable to the activity of the doxorubicin for (HepG-2) cell line. Furthermore, a number of the afforded triazolopyrimidine glycosides were found potent against cancer cells (MCF-7). Furthermore, docking simulation the promising thienopyrimidine analogues 7-13 was done against EGFR kinase to provide a binding model that could serve in discovery of further anticancer agents.

摘要

一系列新的取代三唑并[4,5- d ]嘧啶衍生物与噻吩并嘧啶环系统相连，作为杂环系统，作为可能的核碱基类似物，从关键的羧酰胺衍生物2及其叠氮化物前体开始，通过杂环化反应及其结构进行了表征。对制备的三唑并嘧啶衍生物进行糖基化，并以良好的产率区域选择性地提供相应的噻吩并嘧啶-三唑并嘧啶杂合N ¹ -糖苷及其硫代糖苷类似物。研究了合成的糖基杂环对 HepG-2 和 MCF-7 人癌细胞的细胞毒活性，并获得了显着的结果。化合物7a、8 b、9 b、9a和7 b显示出与多柔比星对 (HepG-2) 细胞系的活性相当的有希望的活性。此外，发现许多提供的三唑并嘧啶糖苷对癌细胞 (MCF-7) 有效。此外，对接模拟有前景的噻吩并嘧啶类似物7-13针对 EGFR 激酶进行，以提供可用于发现更多抗癌剂的结合模型。