Electrochemical Properties of Fused Pyrimidine-Triazole Heterocyclic Molecules as Novel Drug Candidates.

Abstract

Triazolopyrimidinones are compounds used in medicinal chemistry. In this study, three novel triazolopyrimidinone derivatives were synthesized as drug candidates: (5-(chloromethyl)-2-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one) (S1-TP), 2-(4-methoxyphenyl)-5-(piperidinomethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one) (S2-TP), and 2-(4-methoxyphenyl)-5-(morpholinomethyl)-[1,2,4]triazolo[1,5-a] pyrimidin-7(3H)-one) (S3-TP). Their electrochemical properties were investigated for the first time using voltammetric techniques on carbon graphite electrodes. Moreover, stability tests for each drug candidate were performed on different days. After revealing the electrochemical properties of the drug candidates, their effect on double-stranded (ds) DNA was examined by measuring the oxidation currents of the guanine of dsDNA before and after the interaction. An electrochemical setup that included a pencil graphite electrode as the working electrode, an Ag/AgCl reference electrode, and a platinum wire as the auxiliary electrode was used in this study. Experiments for optimum pH, scan rate, and concentration of drug candidates were conducted. The interaction between Ss-TP and dsDNA was evaluated using differential pulse voltammetry. The stability of each drug candidate was tested on various days. A comprehensive characterization of the S1-TP, S2-TP, and S3-TP compounds was performed for the first time. This study showed that the electrochemical oxidation of S1-TP and S2-TP was irreversible and diffusion-controlled. In addition, the transfer of electrons in S3-TP was controlled by adsorption. The interaction between Ss-TP and dsDNA resulted in notable changes in the peak potentialof dsDNA. The dsDNA peak potential shifted negatively after interaction with S1-TP, S2-TP, and S3-TP. Under optimum conditions, the detection limits for S1-TP, S2-TP, and S3-TP were 1.5 µg/mL, 1.0 µg/mL, and 2.0 µg/mL, respectively. From our experimental data, we concluded that these molecules can be used as drug molecules because of their remarkable effects on DNA.