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Synthesis, enzyme inhibitory kinetics mechanism and computational study of N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides as novel therapeutic agents for Alzheimer's disease.
PeerJ. 2018; 6:e4962.P

Abstract

The present study comprises the synthesis of a new series of sulfonamides derived from 4-methoxyphenethylamine (1). The synthesis was initiated by the reaction of 1 with 4-methylbenzenesulfonyl chloride (2) in aqueous sodium carbonate solution at pH 9 to yield N-(4-methoxyphenethyl)-4-methylbenzensulfonamide (3).This parent molecule 3 was subsequently treated with various alkyl/aralkyl halides, (4a-j), using N,N-dimethylformamide (DMF) as solvent and LiH as activator to produce a series of new N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides (5a-j). The structural characterization of these derivatives was carried out by spectroscopic techniques like IR, 1H-NMR, and 13C-NMR. The elemental analysis data was also coherent with spectral data of these molecules. The inhibitory effects on acetylcholinesterase and DPPH were evaluated and it was observed that N-(4-Methoxyphenethyl)-4-methyl-N-(2-propyl)benzensulfonamide (5c) showed acetylcholinesterase inhibitory activity 0.075 ± 0.001 (IC50 0.075 ± 0.001 µM) comparable to Neostigmine methylsulfate (IC50 2.038 ± 0.039 µM).The docking studies of synthesized ligands 5a-j were also carried out against acetylcholinesterase (PDBID 4PQE) to compare the binding affinities with IC50 values. The kinetic mechanism analyzed by Lineweaver-Burk plots demonstrated that compound (5c) inhibits the acetylcholinesterase competitively to form an enzyme inhibitor complex. The inhibition constants Ki calculated from Dixon plots for compound (5c) is 2.5 µM. It was also found from kinetic analysis that derivative 5c irreversible enzyme inhibitor complex. It is proposed on the basis of our investigation that title compound 5c may serve as lead structure for the design of more potent acetylcholinesterase inhibitors.

Authors+Show Affiliations

College of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, South Korea. Department of Chemistry, Government College University, Lahore, Pakistan.College of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, South Korea.Department of Chemistry, Government College University, Lahore, Pakistan.Department of Chemistry, Government College University, Lahore, Pakistan.Faculty of Pharmacy, Universiti Teknologi MARA, Selangor Darul Ehsan, Malaysia. Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Universiti Teknologi MARA, Selangor Darul Ehsan, Malaysia.College of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, South Korea.College of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, South Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29967717

Citation

Abbasi, Muhammad Athar, et al. "Synthesis, Enzyme Inhibitory Kinetics Mechanism and Computational Study of N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides as Novel Therapeutic Agents for Alzheimer's Disease." PeerJ, vol. 6, 2018, pp. e4962.
Abbasi MA, Hassan M, Aziz-Ur-Rehman , et al. Synthesis, enzyme inhibitory kinetics mechanism and computational study of N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides as novel therapeutic agents for Alzheimer's disease. PeerJ. 2018;6:e4962.
Abbasi, M. A., Hassan, M., Aziz-Ur-Rehman, ., Siddiqui, S. Z., Shah, S. A. A., Raza, H., & Seo, S. Y. (2018). Synthesis, enzyme inhibitory kinetics mechanism and computational study of N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides as novel therapeutic agents for Alzheimer's disease. PeerJ, 6, e4962. https://doi.org/10.7717/peerj.4962
Abbasi MA, et al. Synthesis, Enzyme Inhibitory Kinetics Mechanism and Computational Study of N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides as Novel Therapeutic Agents for Alzheimer's Disease. PeerJ. 2018;6:e4962. PubMed PMID: 29967717.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis, enzyme inhibitory kinetics mechanism and computational study of N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides as novel therapeutic agents for Alzheimer's disease. AU - Abbasi,Muhammad Athar, AU - Hassan,Mubashir, AU - Aziz-Ur-Rehman,, AU - Siddiqui,Sabahat Zahra, AU - Shah,Syed Adnan Ali, AU - Raza,Hussain, AU - Seo,Sung Yum, Y1 - 2018/06/26/ PY - 2018/02/14/received PY - 2018/05/20/accepted PY - 2018/7/4/entrez PY - 2018/7/4/pubmed PY - 2018/7/4/medline KW - Acetylcholinesterase KW - Alkyl/aralkyl halides KW - Molecular docking KW - Spectral analysis KW - Sulfonamides SP - e4962 EP - e4962 JF - PeerJ JO - PeerJ VL - 6 N2 - The present study comprises the synthesis of a new series of sulfonamides derived from 4-methoxyphenethylamine (1). The synthesis was initiated by the reaction of 1 with 4-methylbenzenesulfonyl chloride (2) in aqueous sodium carbonate solution at pH 9 to yield N-(4-methoxyphenethyl)-4-methylbenzensulfonamide (3).This parent molecule 3 was subsequently treated with various alkyl/aralkyl halides, (4a-j), using N,N-dimethylformamide (DMF) as solvent and LiH as activator to produce a series of new N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides (5a-j). The structural characterization of these derivatives was carried out by spectroscopic techniques like IR, 1H-NMR, and 13C-NMR. The elemental analysis data was also coherent with spectral data of these molecules. The inhibitory effects on acetylcholinesterase and DPPH were evaluated and it was observed that N-(4-Methoxyphenethyl)-4-methyl-N-(2-propyl)benzensulfonamide (5c) showed acetylcholinesterase inhibitory activity 0.075 ± 0.001 (IC50 0.075 ± 0.001 µM) comparable to Neostigmine methylsulfate (IC50 2.038 ± 0.039 µM).The docking studies of synthesized ligands 5a-j were also carried out against acetylcholinesterase (PDBID 4PQE) to compare the binding affinities with IC50 values. The kinetic mechanism analyzed by Lineweaver-Burk plots demonstrated that compound (5c) inhibits the acetylcholinesterase competitively to form an enzyme inhibitor complex. The inhibition constants Ki calculated from Dixon plots for compound (5c) is 2.5 µM. It was also found from kinetic analysis that derivative 5c irreversible enzyme inhibitor complex. It is proposed on the basis of our investigation that title compound 5c may serve as lead structure for the design of more potent acetylcholinesterase inhibitors. SN - 2167-8359 UR - https://www.unboundmedicine.com/medline/citation/29967717/Synthesis_enzyme_inhibitory_kinetics_mechanism_and_computational_study_of_N__4_methoxyphenethyl__N__substituted__4_methylbenzenesulfonamides_as_novel_therapeutic_agents_for_Alzheimer's_disease_ L2 - https://doi.org/10.7717/peerj.4962 DB - PRIME DP - Unbound Medicine ER -
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