2D-QSAR Modeling, Docking, Synthesis and In-Vitro Evaluation of Novel Flavone Derivatives as Anticancer Agents

Abstract

Background: Cancer is the second leading cause of death globally and is responsible for 10 million deaths in 2020 (2.26 million breast cancer deaths). Due to the problems like drug resistance, toxicities and economic burden, there is a need for the development of novel anticancer agents. Objectives: To design novel flavone derivatives by 2D QSAR studies and docking studies and to evaluate the compounds as potential anticancer agents against MCF7 cell line by MTT assay. Methods: We designed a series of novel flavone derivatives by 2D QSAR modelling using the software QSARINS.The molecular docking studies were carried out to study the molecular interaction and binding affinitiesof the designed compounds against tyrosine protein kinase (PDB ID: 2SRC) by Auto DockVina software. ADMET profiles were calculated for all the designed compounds and five compounds were chosen for synthesis.The synthesized compounds were characterized and evaluated in vitro for anticancer activity against MCF7 cell line by MTT assay. Based on 2D QSAR and molecular docking studies, compounds 3c, 3f, 3i and 3m were synthesized and evaluated for anticancer activity against MCF-7 cell lines. Results: Molecular docking studies of the compounds showed good binding affinity against tyrosine- protein kinase (2SRC). The synthesized flavone derivatives were evaluated for anti-cancer activity against human breast cancer cell line MCF-7 by MTT assay using cisplatin as a positive control. The novel flavone derivative (3c) exhibits more cytotoxicity effect, and the IC50 value of the compound was found to be 52.03 μg/ml. Optimization of these novel scaffolds requires extensive studies on more derivatives. Conclusion: The novel flavone derivatives will be good lead compounds targeting breast cancer.