Síntese e avaliação citotóxica de derivados 1,3,4- oxadiazólicos

Abstract

The synthesis of organic compounds plays a fundamental role in the research of new drugs for various pathologies, since different classes of organic compounds have shown promising biological effects, specially, among these compounds, heterocycles, for their biological versatility. The oxadiazoles are highlighted in this work, which show promising activity when compared to the activity of drugs already used in chemotherapy treatment. This work consisted of the synthesis and evaluation of the cytotoxic activity of phenylsubstituted 1,3,4-oxadiazole derivatives at positions 2 and 5, varying the halogen substitution pattern. Eleven oxadiazoles were obtained starting from a synthetic route initiated by the oxidation of aldehydes to obtain the corresponding carboxylic acids, followed by esterification and hydrozinolysis to form the hydrazides. Once the hydrazides were obtained, they were subjected to reaction with the respective commercial aldehydes to form the N-acylhydrazone intermediate. Finally, the N-acylhydrazone intermediate is subjected to dehydration in a basic medium, with I2 and DMSO for the formation of oxadiazoles. All synthesized compounds had their structures elucidated through infrared and 1H and 13C NMR spectra. All compounds were evaluated for antitumor activity through the cytotoxicity assay against 4T1, CT26-WT and BHK-21 cell lines and IC50 determination. The presented values IC50 ranging from 19-94 µM. In general, the oxadiazoles with para-substituted aromatic rings were the most active, however, when comparing the oxadiazoles with rings having only chlorine as substituents, the meta position in both rings was shown to favor the cytotoxic action. In this work, the results of the cytotoxic action of the evaluated oxadiazoles were relevant to draw a structure-activity profile, also comparing with results already obtained by the research group.