title: Novel biphenyl bis-sulfonamides as acetyl and butyrylcholinesterase inhibitors: Synthesis, biological evaluation and molecular modeling studies.
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.
authors.affiliation: Department of Chemistry, Government College University, Lahore 54000, Pakistan.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Mutahir
authors.affiliation: Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Cracow, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Jończyk
authors.affiliation: Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Cracow, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bajda
authors.affiliation: Department of Chemistry, Government College University, Lahore 54000, Pakistan. Electronic address: iuklodhi@yahoo.com.
authors.forename: Islam Ullah
authors.initials: IU
authors.lastname: Khan
authors.affiliation: Department of Chemistry, Government College University, Lahore 54000, Pakistan.
authors.forename: Muhammad Asim
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Department of Chemistry, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia.
authors.forename: Nisar
authors.initials: N
authors.lastname: Ullah
authors.affiliation: Department of Chemistry, and Department of Biochemistry & Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ashraf
authors.affiliation: Department of Chemistry, and Department of Biochemistry & Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.lastname: Qurat-ul-Ain
authors.affiliation: Department of Chemistry, Government College University, Lahore 54000, Pakistan.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Riaz
authors.affiliation: Department of Chemistry, Government College University, Lahore 54000, Pakistan.
authors.forename: Sajjad
authors.initials: S
authors.lastname: Hussain
authors.affiliation: Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000, Pakistan. Electronic address: drmyar@ciitlahore.edu.pk.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Yar
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D010830:Physostigmine / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014101:Torpedo; D000096926:Benzenesulfonamides
chemical_list: D000110:Acetylcholinesterase; D001713:Biphenyl Compounds; D002091:Butyrylcholinesterase; D002800:Cholinesterase Inhibitors; D010830:Physostigmine; D013449:Sulfonamides; C000613597:N,N'-(3,3'-dimethylbiphenyl-4,4'-diyl)bis(N-benzylbenzenesulfonamide); D000096926:Benzenesulfonamides; C000613596:N,N'-(3,3'-dimethylbiphenyl-4,4'-diyl)bis(N-hexadecylbenzenesulfonamide); C000613598:N,N'-(biphenyl-4,4'-diyl)bis(N-hexadecylbenzenesulfonamide)
keywords: Acetylcholinesterase; Alzheimer’s disease; Biphenyl sulfonamides; Butyrylcholinesterase