Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations

Universidade Federal do Amapá. Departamento de Ciências Biológicas e da Saúde. Macapá, AP, Brasil.Universidade Federal do Amapá. Departamento de Ciências Biológicas e da Saúde. Macapá, AP, Brasil.Universidade Federal do Amapá. Departamento de Ciências Biológicas e da Saúde. Macapá, AP, Brasil.Universidade Federal do Amapá. Departamento de Ciências Biológicas e da Saúde. Macapá, AP, Brasil.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Ribeirão Preto, SP, Brasil.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Ribeirão Preto, SP, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Universidade Federal do Amapá. Colegiado de Química. Macapá, AP, Brasil.Centro Brasileiro de Pesquisas Físicas. Urca, RJ, Brasil.Universidade Federal do Amapá. Colegiado de Química. Macapá, AP, Brasil.Universidade Federal do Amapá. Departamento de Ciências Biológicas e da Saúde. Macapá, AP, Brasil.Glioblastoma is an aggressive primary tumor of the central nervous system (CNS). Is the most aggressive among infiltrative gliomas arising from the CNS. This tumor has low patient survival rate and several studies aiming at developing new drugs have increased. Patients with this cancer type face significant morbidity and mortality. This study evaluated the antineoplastic activity of synthetic chalcones (3a-3f) using in vitro glioblastoma models and molecular modeling. Cytotoxicity assay showed that Astrocitoma Hospital Ofir Loyola No 1 (AHOL1) and Uppsala 87 neoplastic glioblastoma lines (U87) cellular viability were significantly reduced compared to Healthy human fibroblasts cell lines (AN27) when exposed to chalcones. Interaction with the serine amino acid was present in the most promising and the reference binder docking, suggesting its importance inhibiting cell growth. Comparative analysis between the reference ligands and the molecules showed that the amino acid LYS352 present in all fittings, suggesting that this is the main amino acid for interaction with tubulin and are consistent with those in cytotoxicity assay, suggesting antineoplastic potential in glioblastoma. Long trajectory molecular dynamics studies were also carried out in order to investigate stability and conformations amongst the chalcones bound tubulin as well, in comparison to doxorubicin (here used as control), however future studies are needed to further assess the mechanism of inhibition of chalcones used in this investigation