1,3-di-4-piperidylpropane derivatives as potential acetyl cholinesterase antagonists: Molecular docking, synthesis, and biological evaluation | Pakistan Journal of Pharmaceutical Sciences 2021

Ahsaan Ahmed Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Pakistan; Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, Jinnah Sindh Medical University, Karachi, Pakistan

Shamim Akhtar Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University,Karachi,Pakistan

Nousheen Mushtaq Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Pakistan

Shazia Haider Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Pakistan

Rabya Munawar Department of Pharmaceutical Chemistry, Dow College of Pharmacy, Dow University of Health Sciences,Karachi,Pakistan

Hassaan Ahmed Siddique Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Pakistan; Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, Jinnah Sindh Medical University, Karachi, Pakistan

Arifa Akram Department of Pharmaceutical Chemistry, Dow College of Pharmacy, Dow University of Health Sciences,Karachi,Pakistan

Zafar Saeed Saify ICCBS, HEJ Research Institute of Chemistry, University of Karachi,Karachi,Pakistan

Muhammad Arif Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, Karachi, Pakistan

Acetylcholine esterase (AChE) is a key biological target responsible for the management of cholinergic transmission, and its inhibitors are used for the therapy of Alzheimer's disease. In the present study, a small library of molecules with 1,3-di-4-piperidylpropane nucleus were docked on AChE. The selected compounds were synthesized and evaluated for their enzyme inhibition. P25 and P17 expressed significantly higher AChE inhibition than standards with IC50 values of 0.591µM and 0.625µM, respectively. Binding mode of derivatives in the active site of AChE revealed dual binding of molecules in peripheral anionic site (PAS) and catalytic anionic site (CAS) of enzyme cavity.