Bioprospecção de compostos naturais, sintéticos e derivados bioativos com potencial anticancerígeno e imunomodulador

Abstract

Introduction: the resulting toxicity of available therapies against neoplasms continues to be a highly debilitating factor for patients. Medicinal plants and synthetic derivatives have been sources of discovery of several compounds with antineoplastic, anti-inflammatory and analgesic activities. Objective: this study aimed to evaluate the in vitro anticancer and immunomodulatory activity of bioactive and synthetic derivatives against leukemia cell lines. Material and methods: HL60 (acute myeloid leukemia) and K562 (chronic myeloid leukemia) cancer cell lines were used, as well as human peripheral blood mononuclear cells (PBMC) and Vero (kidney epithelium from Cercopithecus aethiops). The evaluation of the cytotoxicity of the compounds was performed using the MTT cell viability test. Cell cycle assays were conducted to determine the effect of the compounds on different stages of the cell cycle. The action of the compounds on the clonal growth of cancerous strains was evaluated using the colony formation test. Immunomodulatory activity was determined by measuring pro and anti-inflammatory cytokines and the ability to inhibit cyclooxygenase 1 and 2 (COX-1 and COX-2) in human PBMC or HL60 cells previously treated with different concentrations of compounds. Results and conclusion: In total, the cytotoxic effects of 11 compounds were evaluated, in which 3 showed selective cytotoxic effects against cancerous strains. Of these, two synthetic compounds, a new synthesis of pyrimidine and a new derivative of spiroindolones, and a natural one, a fraction enriched with polyphenol extracted from Myrtus communis (PEMC). The new pyrimidine synthesis showed a cytotoxic effect both for HL60 cells (IC50:25.93µg/mL) and for K562 (IC50:10.42 µg/mL), while the spiroindolone derivative has a cytotoxic effect against K562 (IC50:25.27µg/mL). Both compounds also showed an immunomodulatory effect on cytokine stimulation in human PBMCs. The PEMC fraction, on the other hand, showed an antiproliferative effect against HL60 (IC50:19.87µM) and K562 (IC50:29.64µM) strains, also demonstrating a significant anti-inflammatory and healing potential. In conclusion, the compounds identified in this study exhibited promising pharmacological potential as antineoplastic agents in the treatment of myeloid leukemias.