Effect of new azoloazine derivatives with potential antitumor activity on energy metabolism in MCF-7 and Vero cell cultures

Abstract

Introduction. The work presents the results of studying the effects of three new azoloazine derivatives on oxidative glucose metabolism in order to select substances with the most acceptable characteristics for further preclinical study as potential antitumor agents, including for breast cancer chemotherapy.Aim. The aim of the work is to identify the metabolic properties of new azoloazine derivatives in terms of their effect on glucose metabolism using a culture of MCF-7 tumor cells and Vero non-tumor cells.Material and Methods. The testing on cell cultures was the main method used in the work, and all tested compounds were applied in final concentrations from 2.5 μmol/L. The comparison drug was epirubicin in the same concentration. The biochemical techniques included the determination of lactate production using commercial Olvex Diagnosticum kits and the determination of oxygen consumption by cells using the Seahorse XFe24 Analyzer for cellular metabolism. The results were processed statistically.Results. Lactate production in MCF-7 and Vero cell cultures decreased by more than half in the presence of 3-Cyclohexyl4-oxoimidazo[5,1-d]-[1,2,3,5]tetrazine-8-N-piperidinyl-carboxamide, and oxygen consumption decreased by 19-40%, which was the maximum effect among the studied azoloazine derivatives. Diethyl ether of 4-aminoimidazo[5,1-c][1,2,4]triazine-3,8dicarboxylic acid and 4-Amino-8-ethoxycarbonyl-imidazo[5,1-c][1,2,4]triazine-3-N-(p-toluyl)carboxamide were similar in their metabolic effects to the comparison drug epirubicin. They reduced lactate production in MCF-7 and Vero cell culture by a third and by 21–22%, respectively. Oxygen consumption in MCF-7 cell culture decreased by 14–17%, in Vero cell culture it decreased by 18–24%.Conclusion. The data obtained allow us to consider the (3-Cyclohexyl-4-oxoimidazo[5,1-d]-[1,2,3,5]tetrazine-8-N-piperidinylcarboxamide as the leader among new azoloazine derivatives and recommend it for further preclinical study as a potential antitumor agent.