Synthesis, anticancer activity and docking study of quinoline, diazepine, pyrimidine and pyridine derivatives (original) (raw)

New classes of quinoline derivatives 2a, b, 7a, b, diazepine derivatives 3a, b, 8a, b, pyrimidine derivatives 4a, b, 5a, b; 6 had been synthesized, via reactions between visnagine carbaldehyde 1 and different reagents. The structures of the products were elucidated by spectra and elemental analyses. In the present work, the derivative products have been tested, along with reference compounds, for their cytotoxic potential against two tumor cell lines. The anticancer activity results indicated that the products 3b, 5b and 7b showed growth inhibition activity against HEPG2 cell line and products 4b, 6, and 8a showed growth inhibition activity against MCF-7. Moreover, we attempted an in-silico approach to gain insights into their binding modes against cyclin-dependent protein kinase 2 (CDK-2) which is involved in cell cycle, and receptor protein B-cell lymphoma 2 (BCL-2) which is involved in cell apoptosis. These targets were selected based on their key roles in cancer progression via the regulation of the cell cycle and DNA replication. Molecular-docking analyses revealed that compound 4b was the best docked ligand against both targets, as it displayed the lowest binding energy, and critical hydrogen bonds and hydrophobic interactions with the targets.