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

Autor: Amin MJ; Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan., Miana GA; Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan. Electronic address: ga.miana@riphah.edu.pk., Rashid U; Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan. Electronic address: umerrashid@cuiatd.edu.pk., Rahman KM; School of Cancer and Pharmaceutical Sciences, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom. Electronic address: k.miraz.rahman@kcl.ac.uk., Khan HU; Department of Chemistry, University of Science and Technology, Bannu, Pakistan., Sadiq A; Associate Professor, Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara 18000, Dir (L), KP, Pakistan. Electronic address: sadiquom@yahoo.com.
Jazyk: angličtina
Zdroj: Steroids [Steroids] 2020 Jun; Vol. 158, pp. 108599. Date of Electronic Publication: 2020 Feb 29.
DOI: 10.1016/j.steroids.2020.108599
Abstrakt: 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 IC 50 values ranging from 14.40 to 40.37 μM. Similarly, the BChE inhibitory potentials of our compounds were also dominant with IC 50 values between 20.08 and 46.84 μM. In comparison to our compounds, the standard drug galantamine attain IC 50 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.
(Copyright © 2020. Published by Elsevier Inc.)
Databáze: MEDLINE
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