Highly functionalized 2-amino-4H-pyrans as potent cholinesterase inhibitors

Raju Suresh Kumar; Abdulrahman I Almansour; Natarajan Arumugam; Dhaifallah M Al-Thamili; Alireza Basiri; D Kotresha; Thota Sai Manohar; S Venketesh; Mohammad Asad; Abdullah M Asiri

doi:10.1016/j.bioorg.2018.08.009

Highly functionalized 2-amino-4H-pyrans as potent cholinesterase inhibitors

Bioorg Chem. 2018 Dec:81:134-143. doi: 10.1016/j.bioorg.2018.08.009. Epub 2018 Aug 12.

Affiliations

¹ Department of Chemistry, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. Electronic address: sraju@ksu.edu.sa.
² Department of Chemistry, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
³ Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, United States.
⁴ Department of Microbiology, East West Group of Institution, no. 63, Anjananagar, Vishwaneedam post, Bangaluru 560091, Karnataka, India.
⁵ Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, A.P. 515 134, India.
⁶ Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Center of Excellence for Advanced Materials Research (CEAMR), King Abdulaziz University, Jeddah 21589, Saudi Arabia.

PMID: 30121001
DOI: 10.1016/j.bioorg.2018.08.009

Abstract

Novel highly functionalized 2-amino-4H-pyrans were achieved in excellent yields under simple grinding at ambient temperature and were assessed for their potential for treating Alzheimer's disease (AD). The 2-amino-4H-pyran bearing nitro groups on both the aryl rings showed the highest activity, with an IC₅₀ of 1.98 ± 0.09 µM against acetylcholinesterase (AChE) and 10.62 ± 0.21 µM against butyrylcholinesterase (BChE), the inhibition mechanisms on AChE and BChE receptors were revealed by means of molecular docking simulations.

Keywords: 2-amino-4H-pyrans; AChE; Alzheimer’s disease; BChE; Molecular docking simulations.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase / metabolism*
Butyrylcholinesterase / metabolism*
Cholinesterase Inhibitors / chemical synthesis
Cholinesterase Inhibitors / chemistry
Cholinesterase Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Humans
Molecular Docking Simulation
Molecular Structure
Pyrans / chemical synthesis
Pyrans / chemistry
Pyrans / pharmacology*
Structure-Activity Relationship

Substances

Cholinesterase Inhibitors
Pyrans
Acetylcholinesterase
Butyrylcholinesterase