DRUG DESIGN OF CORTICOTROPHIN RELEASING FACTOR RECEPTOR-1 ANTAGONIST FROM DERIVATIVES OF α ASARONE BY MOLECULAR DOCKING

Stress is one of the most significant health problem in modern society. This paves way for the researchers to focus and investigate into the biological pathways linking stress and health. Hence the goal of the present study is to discover novel drug derivatives from the active principle α asarone of the plant Acorus calamus Linn. (ACL) which was found to have antioxidant &antidepressor effect the basic physiological response to stress is through activation of Corticotrophin –releasing factor Receptor 1 (CRFR-1) which is predominantly found in pituitary gland is mainly responsible for signalling the adrenal gland receptor thereby increasing the Glucocorticoids as a response to stress. The 3D structure of CRFR 1 was derived from RCSB-PDB database and the α asarone was derive from Pubchem database. A total of 100 ligands were derived from α asarone using in silico method by ACD chemsketch software. Rapid virtual screening of these compounds were performed in the dock in tool iGEMDOCK v2.0. Based on the binding energy a total of seven ligands were further docked using Auto Dock 4.0 software. The selected seven ligands were then analysed for the drug relevant properties based on “Lipinski’s rule of five” and other drug like properties. Results of the current study showed that one of the derivatives of α asarone namely 4[(hyydroxyethynyl)amino]phenol-methane have shown excellent binding energy valves of -100.26 kcal/mol with a good drug likeliness and drug  score. Hence this compound is a excellent drug candidate in the inhibition of CRFR-1 and can be potentially used to manage the elevated levels of glucocorticoids level during stress.