Synthesis, biological evaluation and molecular simulation studies of new arylated benzo[h]quinolines compounds as potential anticancer agents

D is a major active ingredient and principal component in several plants, Derris trifoliata Lour. (Leguminosae), Mundulea sericea (Leguminosae), Tephrosia vogelii Hook.f. (Leguminosae) and potential molecule to target cancer cell signaling pathway proteins. As a complex natural extract, deguelin interacts with various molecular targets to exert its anti-tumor properties at nanomolar levels. Deguelin induced cell apoptosis by blocking anti-apoptotic pathways, while inhibiting tumor cell propagation and malignant transformation through p27-cyclin-E-pRb-E2F1cell cycle control and HIF-1αVEGF antiangiogenic pathways. Our research explores the deguelin and its derivatives interaction with crystal structure of cyclin D1 (PDB ID: 2W96) and cyclin E (PDB ID: 2AST) to understand the better molecular insights. Molecular modelling of ligands (deguelin and its derivatives) were carried out by Avogadro software till stable confirmation obtained. The partial charges for the ligands were assigned as per standard protocol for molecular docking. All docking simulation were performed with AutoDock Vina on workstation. Virtual screening was done for all docked molecules based on binding energy and hydrogen bonding affinity. Molecular dynamics (MD) and Simulation (10 ns and 12 ns for cyclin D1 and cyclin E1 respectively) was done using GROMACS 5.1.1 software to explore the interaction stability. All the stable confirmations for cyclin D1 and cyclin E proteins trajectories was captured at various time intervals. Few compounds screened based on high affinity as inhibitors for cyclin D1 and cyclin E and may inhibit the cell cycle in cancer cell signaling under in vitro and in vivo experiments.