Novel biphenyl bis-sulfonamides as acetyl and butyrylcholinesterase inhibitors: Synthesis, biological evaluation and molecular modeling studies

Sadaf Mutahir; Jakub Jończyk; Marek Bajda; Islam Ullah Khan; Muhammad Asim Khan; Nisar Ullah; Muhammad Ashraf; Qurat-ul-Ain; Sadaf Riaz; Sajjad Hussain; Muhammad Yar

doi:10.1016/j.bioorg.2015.11.002

Novel biphenyl bis-sulfonamides as acetyl and butyrylcholinesterase inhibitors: Synthesis, biological evaluation and molecular modeling studies

Bioorg Chem. 2016 Feb:64:13-20. doi: 10.1016/j.bioorg.2015.11.002. Epub 2015 Nov 10.

Authors

Affiliations

¹ Department of Chemistry, Government College University, Lahore 54000, Pakistan.
² Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Cracow, Poland.
³ Department of Chemistry, Government College University, Lahore 54000, Pakistan. Electronic address: iuklodhi@yahoo.com.
⁴ Department of Chemistry, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia.
⁵ Department of Chemistry, and Department of Biochemistry & Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
⁶ Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000, Pakistan. Electronic address: drmyar@ciitlahore.edu.pk.

PMID: 26595185
DOI: 10.1016/j.bioorg.2015.11.002

Abstract

A series of new biphenyl bis-sulfonamide derivatives 2a-3p were synthesized in good to excellent yield (76-98%). The inhibitory potential of the synthesized compounds on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was investigated. Most of the screened compounds showed modest in vitro inhibition for both AChE and BChE. Compared to the reference compound eserine (IC50 0.04 ± 0.0001 μM for AChE) and (IC50 0.85 ± 0.0001 μM for BChE), the IC50 values of these compounds were ranged from 2.27 ± 0.01 to 123.11 ± 0.04 μM for AChE and 7.74 ± 0.07 to <400 μM for BuChE. Among the tested compounds, 3p was found to be the most potent against AChE (IC50 2.27 ± 0.01 μM), whereas 3g exhibited the highest inhibition for BChE (IC50 7.74 ± 0.07 μM). Structure-activity relationship (SAR) of these compounds was developed and elaborated with the help of molecular docking studies.

Keywords: Acetylcholinesterase; Alzheimer’s disease; Biphenyl sulfonamides; Butyrylcholinesterase.

Publication types

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

MeSH terms

Acetylcholinesterase / metabolism*
Animals
Biphenyl Compounds / chemical synthesis
Biphenyl Compounds / chemistry
Biphenyl Compounds / pharmacology*
Butyrylcholinesterase / metabolism*
Cholinesterase Inhibitors / chemical synthesis
Cholinesterase Inhibitors / chemistry
Cholinesterase Inhibitors / pharmacology*
Humans
Molecular Docking Simulation
Physostigmine / pharmacology
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry
Sulfonamides / pharmacology*
Torpedo

Substances

Biphenyl Compounds
Cholinesterase Inhibitors
N,N'-(3,3'-dimethylbiphenyl-4,4'-diyl)bis(N-benzylbenzenesulfonamide)
N,N'-(3,3'-dimethylbiphenyl-4,4'-diyl)bis(N-hexadecylbenzenesulfonamide)
N,N'-(biphenyl-4,4'-diyl)bis(N-hexadecylbenzenesulfonamide)
Sulfonamides
Physostigmine
Acetylcholinesterase
Butyrylcholinesterase