SAR based in-vitro anticholinesterase and molecular docking studies of nitrogenous progesterone derivatives

Abstract

Progesterone is a steroidal hormone that has been described with pathogenic features of brain dysfunction, realized with advanced age-related neurodegenerative diseases such as Alzheimer's disease. In this study, sixteen nitrogenous derivatives of progesterone which we previously synthesized have been used for Alzheimer targets. The progesterone derivatives (1-16) were screened for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potentials in a dose-dependent manner. All the compounds exhibited overwhelming AChE inhibitions, with IC₅₀ values ranging from 14.40 to 40.37 μM. Similarly, the BChE inhibitory potentials of our compounds were also dominant with IC₅₀values between 20.08 and 46.84 μM. In comparison to our compounds, the standard drug galantamine attain IC₅₀ values of 12.03 and 18.20 μM against AChE and BChE respectively. Molecular docking studies suggested that the compounds exerted their inhibitory activity by binding to the active site of the enzyme. The cholinergic system plays an important role in the regulation of learning and memory processes and has been a major target for the design of anti-Alzheimer's drugs. Therefore, these nitrogen-containing progesterone derivatives will be of potential interest to researchers working in AD for developing new drugs or chemical tools to study the disease.

Keywords: Alzheimer disease; Anticholinesterase; Molecular docking; Progesterone.