Avaliação da atividade antineoplásica de chalconas sintéticas utilizando modelos de glioblastomas in vitro e docking molecular para topoisomerase-II-α e tubulina

Abstract

Introduction: Glioblastoma is a malignant tumor with low survival rate, has rapid growth and has a high turnover rate. Studies aiming at the development of new anticancer drugs have increased, predicting the mode of anchoring promising molecules to the site of interest is paramount in rational drug design. Purpose: This study evaluated the antineoplastic activity of synthetic chalcones using in vitro glioblastomas models and proposed by molecular docking the site of action of these molecules. Methodology: chalcones were synthesized and analyzed by gas chromatography coupled to the mass spectra, cell viability was investigated by the MTT test and the molecular docking study was performed in the GOLD software. Results and discussion: The results of the MTT assay showed that the AHOL1 and U87 cells had their cell viability reduced when the chalcones analyzed were exposed, presenting a significant difference (p <0.0001) when compared to the AN27 healthy lineage. The comparative analysis of the interactions of the molecules with the TOPIIA target identified interactions in serine (SER148-149) and isoleucine (ILE125). Interaction with the serine amino acid was present in both the most promising and the reference binder docking, suggesting its importance in the inhibitory effect of cell growth. Comparative analysis between the reference ligands and the molecules in studies identified the amino acid LYS 352 present in all of the inserts, suggesting that this is the main amino acid for interaction with tubulin, it was also observed that the absence of interaction with the amino acid CYS 241 causes reduction in the gold score. Conclusions: The results obtained in the molecular docking corroborate with that observed in MTT, suggesting that the molecules under study have antineoplastic potential in glioblastomas