Discovery of Potential Inhibitors for SFRP3: Ligand-Based 3D Pharmacophore, Virtual Screening, Molecular Docking, and Dynamics Studies

Abstract

Cancer is a complicated and diverse family of diseases characterized by the body’s aberrant cells growing and spreading out of control. It is one of the major causes of mortality in the world and may affect almost every organ or tissue in the body. One of the most prevalent forms of malignant tumors that affect both men and women is bone cancer. The study introduces the soluble frizzled-related protein SFRP3 as a significant participant. It functions as a tumor suppressor and regulator as well as an antagonist of the Wnt signaling pathway. It interacts directly with Wnts, regulating Wnt signaling and directing cell proliferation and differentiation in certain cell types. The study focuses on SFRP3 as a possible target for bone cancer therapy. The purpose is to find prospective medication candidates. Several databases are listed as possible drug compound sources, including NCI_Natural Products, Enamine, and specifications. Potent drugs from the selected databases are scrutinized and identified using ligand-based pharmacophore modeling. The binding affinity and interactions between the selected compounds and the SFRP3-modeled protein are evaluated using virtual screening and molecular docking approaches. The selection of lead compounds is based on their scores, binding affinity, and interactions, which indicate their potential as therapeutic candidates. To ensure that the contacts stay stable throughout time, molecular dynamics modeling is used to analyze the stability of the Protein-Ligand complex. The investigation leads to the identification of the top three compounds from each of the three databases that show potential against the target protein, SFRP3.