A new attempt to introduce efficient inhibitors for Caspas-9 according to structure-based Pharmacophore Screening strategy and Molecular Dynamics Simulations

Document Type: Research Paper

Authors

1 Postgraduate Researcher ACROSS ​Centre (Australian Centre for Research on Separation Science) University of Tasmania Hobart​, Australia

2 Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Medical Sciences, University of Tehran 14155-6451, Iran

Abstract

Caspases are enzymes which are the main pathway for apoptosis. Any irregulation in their functions causes increase or decrease cell death which result in autoimmune or cancer respectively. Structure-based pharmacophore drug discovery method was used to discover selective inhibitors for Caspase-9 as the initiator Caspase through effective pathway in Alzheimer’s disease, through virtual screening. A pharmacophore model was developed by investigating essential interactions between the reported potent inhibitors employing a docking analysis methodology. After pharmacophore virtual screening, 9 compounds from both National Cancer Institute (NCI) and ZINC databases were filtered as potent inhibitors of Caspase-9. The efficiency of the discovered compounds was further monitored by docking studies.

Graphical Abstract

A new attempt to introduce efficient inhibitors for Caspas-9 according to structure-based Pharmacophore Screening strategy and Molecular Dynamics Simulations

Keywords