Screening of Potential Breast Cancer Inhibitors through Molecular Docking and Molecular Dynamics Simulation

Cyclooxygenase-2 (COX-2) is a key enzyme involved in overexpression in several human cancerous diseases including breast cancer. By performing efficient virtual screening in a series of active molecules or compounds from the Maybridge, NCI (National Cancer Institute), and Enamine databases, potential identification of COX-2 inhibitors could lead to new prognostic strategies in the treatment of breast cancer. Based on a 50% structural similitude, compounds were chosen as the inductive model of COX-2 inhibitions from these databases. Selected compounds were filtered and tested with Lipinski's rule of five followed by absorption, distribution, metabolism, and excretion (ADME) properties. Subsequently, molecular docking was performed to achieve accuracy in screening and also to find an interactive mechanism between hit compounds with their respective binding sites. Simultaneously, molecular simulations of top-scored compounds were selected and coded such as Maybridge_55417, NCI_30552, and Enamine_62410. Chosen compounds were analyzed and interpreted with COX-2 affinity. Results endorsed that hydrophobic affinity and optimum hydrogen bonds were the forces driven in the interactive mechanism of in silico hits compounds with COX-2 and can be used as efficient alternative therapeutic agents targeting deleterious breast cancer. With these in silico findings, compounds identified may prevent the action of the COX-2 enzyme and thereby diminish the incidence of breast cancer.