SYNTHESIS OF DIHYDROTETRAZOLOPYRIMIDINE DERIVATIVES AS ANTICANCER AGENTS AND INHIBITOR OF α-GLUCOSIDASE

Abstract

A series of dihydrotetrazolopyrimidine derivatives were prepared to utilize a three-component Biginelli reaction from ethyl 3-oxo butanoate, 5-amino tetrazole, and various aromatic aldehydes as reactants, pTSA as a Brønsted acid catalyst, and ethanol as the solvent. The structure of the prepared compounds was established by spectroscopic evidence, FTIR, HRMS, and NMR (1 H-and13 C-) spectra. The electronic properties of the aromatic aldehyde's substituents affected the reaction's time and yield. Substituents possessing electron-donating character accelerated the reaction time but decreased the reaction yield, whereas substituents with electron-withdrawing properties slowed the reaction but increased the yield. The prepared compounds exhibited moderate to strong anti-proliferative activities against 4T1 and HeLa cancer cell lines. Compound Ethyl (E)-5-methyl-7-(1-phenylprop-1-en-2-yl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate and compound Ethyl 7-(1H-indol-3-yl)-5-methyl-4,7-dihydrote-trazolo[1,5-a]pyrimidine-6-carboxylate) showed strong anti-proliferative activities in vitro through induction apoptotic cells death mechanism. In addition, five of the synthesized compounds exhibited better inhibitory activity of α-glucosidase than quercetin, the positive control.