Synthesis, enzyme inhibitory kinetics mechanism and computational study of N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides as novel therapeutic agents for Alzheimer’s disease
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-methylbenzensu...
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PeerJ Inc.
2018-06-01
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| Online Access: | https://peerj.com/articles/4962.pdf |
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| author | Muhammad Athar Abbasi Mubashir Hassan Aziz-ur-Rehman Sabahat Zahra Siddiqui Syed Adnan Ali Shah Hussain Raza Sung Yum Seo |
| author_facet | Muhammad Athar Abbasi Mubashir Hassan Aziz-ur-Rehman Sabahat Zahra Siddiqui Syed Adnan Ali Shah Hussain Raza Sung Yum Seo |
| author_sort | Muhammad Athar Abbasi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T07:03:39Z |
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| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T07:03:39Z |
| publishDate | 2018-06-01 |
| publisher | PeerJ Inc. |
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| spelling | doaj.art-dfc654fbcece4530929d2fe73df2272a2023-12-03T09:47:15ZengPeerJ Inc.PeerJ2167-83592018-06-016e496210.7717/peerj.4962Synthesis, enzyme inhibitory kinetics mechanism and computational study of N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides as novel therapeutic agents for Alzheimer’s diseaseMuhammad Athar Abbasi0Mubashir Hassan1Aziz-ur-Rehman2Sabahat Zahra Siddiqui3Syed Adnan Ali Shah4Hussain Raza5Sung Yum Seo6College of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, South KoreaCollege of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, South KoreaDepartment of Chemistry, Government College University, Lahore, PakistanDepartment of Chemistry, Government College University, Lahore, PakistanFaculty of Pharmacy, Universiti Teknologi MARA, Selangor Darul Ehsan, MalaysiaCollege of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, South KoreaCollege of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, South KoreaThe 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.https://peerj.com/articles/4962.pdfSulfonamidesMolecular dockingAcetylcholinesteraseAlkyl/aralkyl halidesSpectral analysis |
| spellingShingle | Muhammad Athar Abbasi Mubashir Hassan Aziz-ur-Rehman Sabahat Zahra Siddiqui Syed Adnan Ali Shah Hussain Raza Sung Yum Seo 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 Sulfonamides Molecular docking Acetylcholinesterase Alkyl/aralkyl halides Spectral analysis |
| title | Synthesis, enzyme inhibitory kinetics mechanism and computational study of N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides as novel therapeutic agents for Alzheimer’s disease |
| title_full | Synthesis, enzyme inhibitory kinetics mechanism and computational study of N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides as novel therapeutic agents for Alzheimer’s disease |
| title_fullStr | Synthesis, enzyme inhibitory kinetics mechanism and computational study of N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides as novel therapeutic agents for Alzheimer’s disease |
| title_full_unstemmed | Synthesis, enzyme inhibitory kinetics mechanism and computational study of N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides as novel therapeutic agents for Alzheimer’s disease |
| title_short | Synthesis, enzyme inhibitory kinetics mechanism and computational study of N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides as novel therapeutic agents for Alzheimer’s disease |
| title_sort | synthesis enzyme inhibitory kinetics mechanism and computational study of n 4 methoxyphenethyl n substituted 4 methylbenzenesulfonamides as novel therapeutic agents for alzheimer s disease |
| topic | Sulfonamides Molecular docking Acetylcholinesterase Alkyl/aralkyl halides Spectral analysis |
| url | https://peerj.com/articles/4962.pdf |
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