A Combination of Pharmacophore Modeling, Molecular Docking and Virtual Screening Study Reveals 3,5,7-Trihydroxy-2-(3,4,5-trihydroxyphenyl)- 4H-Chromen-4-One as a Potential Anti-Cancer Agent of COT Kinase

Background: COT (Tpl2/MAP3K8) is a Serine/ Threonine protein kinase which plays a crucial role in the production of TNF-alpha through the phosphorylation of MEK, ERK pathway and the production of other pro-inflammatory cytokines. Its inhibition has been shown as important to reduce inflammatory diseases and cancer. Material and Methods: Combined Ligand-based and Structure-based pharmacophore model was developed for finding out the potential anticancer agents. These combined pharmacophore model was used as 3D-query for searching the matching pharmacophore features against chemical structure databases such as DrugBank, MDPI, ZINC, Maybridge HitFinder. Docking was performed using Schrodinger software as well as selected Hits were filtered by ADMET properties. Results: Among all the selected Hits Compound 3,5,7-trihydroxy-2-(3,4,5- trihydroxyphenyl)-4H-chromen-4-one was found to be more potent according to the docking score. Conclusion: A step by step computational pipeline was used to find out the potential anticancer agents. This study suggests that these Hits could be used as anticancer agents against death leading diseases.