Síntese de 1,3,4-oxadiazóis acoplados a piperazina alquilada e avaliação da ação citotóxica em modelos in vitro de linhagens de tumores animais

Abstract

In 2020 cancer still remains one of the leading causes of death in the world. Since the treatments and drugs used still have a low selectivity and cause various side effects in patients, it is important to continue scientific studies to propose new chemotherapeutic drugs that are more active and more selective that cause fewer adverse effects. With a deficit of effective drugs, this work aimed at the synthesis and characterization of 1,3,4-oxadiazolic derivatives coupled to alkylated piperazines and the evaluation of their cytotoxic activities. Eight new compounds were obtained in a five-step synthesis starting from two different carboxylic acids, which after esterefication and hydrazinolysis of the esters made it possible to obtain hydrazides, which after reaction with bromoacetyl bromide formed the N,N'-diacylhydrazine intermediates that were cyclized to obtain 1,3,4-oxadiazole derivatives. These derivatives were coupled with alkylated piperazines with chains of 8, 10, 12 and 14 carbon atoms. All synthesized compounds were characterized by 1H, 13C and IR NMR spectra. Once the compounds were characterized, their antitumor activities against animal tumor cell lines were evaluated by cytotoxicity to determine IC50 and IS. All the tested compounds obtained cytotoxicity against 4T1 and CT26.WT cell lines, where were obtained CI50 values that varied from 2.6 µM to 72.2 µM with IS from 0.4 to 4.0 for cell line 4T1 and 2.6 µM to 35.2 µM with IS from 1.1 to 2.5 for cell line CT26.WT. Notably, the compounds (7) and (17) synthesized in the present project were more cytotoxic than cisplatin, the positive control used .