Avaliação da atividade citotóxica de derivados de guanilidrazonas em linhagem de glioblastoma humano GBM02

Abstract

Cancer is considered a public health problem and can be associated with the four main causes of death in the world. Among the most aggressive types of cancer are gliomas. Gliomas are considered one of the main types of central nervous system tumors and have high molecular heterogeneity and a large number of genetic mutations, so the development of specific target prototypes is necessary. Guanylhydrazones belong to the class of hydrazones and have several activities in the literature, such as antitumor activity against leukemia, melanoma, lung, kidney and colon cancer. The present work aims to evaluate the in vitro antitumor activity of guanylidrazone derivatives in cells of a human glioblastoma lineage. The cytotoxic effect of guanylidrazones against monocytes and lymphocytes was evaluated by the MTT assay at concentrations of 0,1, 1, 3, 10, 30, 100 µM. To evaluate the antitumor effect of guanylhydrazones, the MTT assay was also performed with cells of the GBM02 lineage, at the same concentrations, where the positive control was Temozolamide (TMZ). The selectivity index was calculated by the formula cytotoxic concentration in 50% of the cells/inhibitory concentration in 50% of the cells. The migration test was performed using Scratch, where microphotographs are used to obtain the migration percentage. For the morphology study, GBM02 cells were plated and adhered to coverslips, with TMZ as a positive control and DMSO 0.2% as a negative control. Regarding the cytotoxicity assay, none of the compounds used in the test showed toxicity against monocytes and lymphocytes and all of them proved to be selective for GBM02 cells. As a result of the in vitro antitumor activity against GBM02, the derivatives compared to the prototype were equipotent, except for LQM 242. Regarding the inhibitory effect, the compounds of the series showed a cytotoxic effect greater than 70%, except for LQM 242 and LQM 244 in 48 hours of treatment. In the Scratch test, it can be seen that the compounds influenced the decrease in GBM02 migration, especially LQM 14, which decreased migration by 88,09% and LQM 240, which decreased by 86,54%. Regarding morphology, the derivatives LQM 14 and LQM 240 morphologically affected the neoplastic cells. In view of the results, it can be observed that this series of compounds demonstrated the ability to be antitumor agents, moving towards the perspective of new studies, mainly of mechanism of action and in vivo, with the objective of becoming future therapeutic options in the treatment of glioblastoma, a tumor that currently has no cure.