Ligand-Based Drug Design of Novel MARK-3 Inhibitors in Cancer

Protein kinases are enzymes that have a key regulatory role in cell biology involved in various cellular processes such as apoptosis, cell cycle, cytoskeletal rearrangement, immune response, nervous system function, and transcription. MARK3 protein kinase was identified as a marker for cancer, and proved to be overexpressed in head and neck cancer. With the aim of identifying possible active compounds able to perform interactions with the MARK3 protein binding site, active substructures known as scaffold were used in the process of similarity search. In this work, ligand-based virtual screening approaches were carried out to investigate potential novel MARK3 inhibitors. The obtained docking poses were rescored and after applying filters related to the physicochemical properties, as well as overlapping molecular interaction fields, toxicity prediction and prediction of biological activity spectra, three compounds were selected as the most promising and potential MARK3 inhibitors, with interest in head and neck cancer. Our results suggest that these molecules could be developed as novel lead compounds in anti-cancer drug design.