Synthesis, anticancer activity and molecular docking of new triazolo[4,5-<i>d</i>]pyrimidines based thienopyrimidine system and their derived <i>N</i>-glycosides and thioglycosides

Abstract

A series of new substituted triazolo[4,5-<i>d</i>]pyrimidine derivatives linked to thienopyrimidine ring system were prepared as a hybrid heterocyclic systems, as possible nucleobases analogs, starting from the key carboxamide derivative <b>2</b> 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 <i>N</i>¹-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 <b>7a</b>, <b>8 b</b>, <b>9 b</b>, <b>9a</b> and <b>7 b</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 <b>7-13</b> was done against EGFR kinase to provide a binding model that could serve in discovery of further anticancer agents.