Synthesis and molecular docking studies of some 4-phthalimidobenzenesulfonamide derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors

Abstract

A series of 4-phthalimidobenzenesulfonamide derivatives were designed, synthesized and evaluated for the inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Structures of the title compounds were confirmed by spectral and elemental analyses. The cholinesterase (ChE) inhibitory activity studies were carried out using Ellman’s colorimetric method. The biological activity results revealed that all of the title compounds (except for compound 8) displayed high selectivity against AChE. Among the tested compounds, compound 7 was found to be the most potent against AChE (IC50= 1.35 ± 0.08 μM), while compound 3 exhibited the highest inhibition against BuChE (IC50= 13.41 ± 0.62 μM). Molecular docking studies of the most active compound 7 in AChE showed that this compound can interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE.

New Hybrids of 4-Amino-2,3-polymethylene-quinoline and p-Tolylsulfonamide as Dual Inhibitors of Acetyl- and Butyrylcholinesterase and Potential Multifunctional Agents for Alzheimer’s Disease Treatment

“…They are also among the most effective and highly investigated derivatives in the field of carbonic anhydrases inhibition and related clinical applications [ 60 , 61 , 62 ]. Recently, publications have appeared on the presence of inhibitory activity against AChE and BChE in various sulfonamide derivatives [ 63 , 64 , 65 , 66 , 67 ]. Sulfonamide-containing selective and reversible human BChE inhibitors with nanomolar potency were developed that improved learning and memory functions in mouse models [ 21 ].…”

Isolation and characterization of novel acetylcholinesterase inhibitors from Ficus benghalensis L. leaves

“…The X-ray crystallographic structure of donepezil in the complex with AChE was retrieved from the Protein Data Bank through the internet (http://www.rcsb.org/, PDB code 1EVE). 26 The enzyme was prepared for docking studies using the following steps: hydrogen atoms were added to the system with their standard geometry. The atom connection and type were checked for any errors with automatic correction.…”

“…Based on the biological evaluation results and to explore the possible binding mode of the isolated compounds with AChE (PDB code 1EVE), 26 docking studies were performed using the Molecular Operating Environment (MOE) package version 2014.10 (Chemical Computing Group, Inc. Molecular Operating Environment (MOE). CCG, Montreal, Canada.2014.…”

Biological Evaluation, Qsar and Molecular Modeling Studies of 2,4-Dichlorobenzoic Acid Derivatives as Antimicrobial Agents

“…Sulfonamides, being antibacterial, having the prominent mechanism of action including attachment of sulfonamides with the dihydropteroate synthetase (DHPS) enzyme and alteration of bacterial pathways of folic acid synthesis in few eukaryotic cells, but in human beings, this mechanism is not followed [3,4]. The sulfonamides have been recognized due to various reported biological activities such as anticancer [5][6][7][8][9], anti-Alzheimer [10,11], anti-tubercular [12,13], antimicrobial [14][15][16][17], anti-inflammatory [18], carbonic anhydrase inhibitors [19][20][21][22], antidiabetic [11], anticonvulsant [23], and antimalarial [24][25][26].…”

“…Due to these facts, there is a prime need to shorten the duration of therapy and ascertain newer antimicrobial agents to avert the emergence of resistance. In continuation of our efforts dedicated toward development of antimicrobials, we have screened compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) reported by Thakral and Singh [27] for antimicrobial potential along with QSAR and computational studies.…”