Novel drug discovery against breast and lung cancer using pharmacophore based 2H-1-benzopyran-2-one derivative
Nidhi Mishra, Akhilesh Kumar Maurya · Research Square · 2022
Abstract With the rising number of cancer patients and the associated cancer resistance pathway, the demand for design of innovative novel drugs has never been greater. Coumarins (2H-1-benzopyran-2-one) are an antibiotic that is effective against a variety of diseases. Breast cancer and lung cancer were the focus of this research. To create a pharmacophore hypothesis, biologically active coumarin derivatives were tested against MCF-7, a breast cancer cell line, and A-549, a lung cancer cell line, using IC50 values. The AAARR 1 theory had the highest score. Both types of cancer were studied using a 3D QSAR model. To determine R2 and Q2 values; the pIC50 of the intended compound were used to generate the 3D-QSAR model which showed excellent predictive and descriptive capacity. The QSAR approach was used to develop 17 new compounds against breast cancer and 23 new compounds for lung cancer. VEGFR-2 (PDB ID: 4ASD) breast cancer protein and Protein kinase C iota (PKCι) lung cancer causing proteins were used to dock with newly designed compounds. The docking data were compared to FDA-approved breast cancer medications Abemaciclib and lung cancer treatments Vinorelbine. Molecular dynamic simulation was used to verify the docking results. The protein's stability was demonstrated using the designed ligand. The research presents a computationally-driven approach in building and finding novel coumarin scaffolds for cancer inhibition.