The Experts below are selected from a list of 48 Experts worldwide ranked by ideXlab platform
Nigel H Greig - One of the best experts on this subject based on the ideXlab platform.
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long acting anticholinesterases for myasthenia gravis synthesis and activities of quaternary phenylcarbamates of Neostigmine pyridostigmine and physostigmine
Bioorganic & Medicinal Chemistry, 2010Co-Authors: Qian Sheng Yu, Harold W Holloway, Debomoy K Lahiri, Arnold Brossi, Nigel H GreigAbstract:The N-monophenylcarbamate analogues of Neostigmine Methyl Sulfate (6) and pyridostigmine bromide (8) together with their precursors (5), (7), and the N(1)-Methylammonium analogues of (−)-phenserine (12), (−)-tolserine (14), (−)-cymserine (16) and (−)-phenethylcymserine (18) were synthesized to produce long-acting peripheral inhibitors of acetylcholinesterase or butyrylcholinesterase. Evaluation of their cholinesterase inhibition against human enzyme ex vivo demonstrated that, whereas compounds 5–8 possessed only marginal activity, 12, 14, 16 and 18 proved to be potent anticholinesterases. An extended duration of cholinesterase inhibition was determined in rodent, making them of potential interest as long-acting agents for myasthenia gravis.
Qian Sheng Yu - One of the best experts on this subject based on the ideXlab platform.
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long acting anticholinesterases for myasthenia gravis synthesis and activities of quaternary phenylcarbamates of Neostigmine pyridostigmine and physostigmine
Bioorganic & Medicinal Chemistry, 2010Co-Authors: Qian Sheng Yu, Harold W Holloway, Debomoy K Lahiri, Arnold Brossi, Nigel H GreigAbstract:The N-monophenylcarbamate analogues of Neostigmine Methyl Sulfate (6) and pyridostigmine bromide (8) together with their precursors (5), (7), and the N(1)-Methylammonium analogues of (−)-phenserine (12), (−)-tolserine (14), (−)-cymserine (16) and (−)-phenethylcymserine (18) were synthesized to produce long-acting peripheral inhibitors of acetylcholinesterase or butyrylcholinesterase. Evaluation of their cholinesterase inhibition against human enzyme ex vivo demonstrated that, whereas compounds 5–8 possessed only marginal activity, 12, 14, 16 and 18 proved to be potent anticholinesterases. An extended duration of cholinesterase inhibition was determined in rodent, making them of potential interest as long-acting agents for myasthenia gravis.
Kelly, Liam P.(liam Porter) - One of the best experts on this subject based on the ideXlab platform.
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Development of a continuous-flow synthesis of Neostigmine MethylSulfate and studies toward a continuous-flow synthesis of lisinopril
Massachusetts Institute of Technology, 2019Co-Authors: Kelly, Liam P.(liam Porter)Abstract:Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2019Cataloged from PDF version of thesis.Includes bibliographical references.[color illustration] Herein, we describe the development of a continuous flow synthesis of Neostigmine Methyl Sulfate, an acetylcholinesterase inhibitor on the WHO list of essential medicines, and the transfer of the synthesis into a next-generation reconfigurable frame developed by our collaborators. Starting from 3-diMethylaminophenol, the synthesis provides a throughput of approximately 46.8 g/day (or 93,600 doses/day) of crude Neostigmine Methyl Sulfate. The synthesis also showcases a prototype in-line evaporation unit that operates without any added carrier gas. Dr. Christina Dai performed early screening of lithium bases. Dr. Yuqing Cui and Dr. Naomi Briggs developed the downstream purification sequence. Dr. Nopphon Weeranoppanant developed the in-line evaporator and, along with Dr. Dale Thomas, assisted with performing the synthesis within their developed frame. Liam P. Kelly developed the continuous synthesis of Neostigmine Methyl Sulfate. [color illustration] Lisinopril is a member of a large family of ACE inhibitors generally known as N-carboxyethyl dipeptides. Of this family, lisinopril is the most commonly prescribed. All known routes to lisinopril require isolation of several synthetic intermediates and protecting group manipulations, thus, development of an efficient continuous synthesis would provide great benefit. Herein we describe our investigation of several routes to generate intermediates of lisinopril with the end goal of a fully continuous synthesis, high material throughput, and minimal protecting group manipulations. Liam P. Kelly performed all work described within this chapter.by Liam P. Kelly.Ph. D.Ph.D. Massachusetts Institute of Technology, Department of Chemistr
Ki Hwan Lee - One of the best experts on this subject based on the ideXlab platform.
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Acetylcholinesterase immobilization and characterization, and comparison of the activity of the porous silicon-immobilized enzyme with its free counterpart
Bioscience reports, 2016Co-Authors: Muhammad Saleem, Muhammad Rafiq, Sung-yum Seo, Ki Hwan LeeAbstract:A successful prescription is presented for acetylcholinesterase physically adsorbed on to a mesoporous silicon surface, with a promising hydrolytic response towards acetylthiocholine iodide. The catalytic behaviour of the immobilized enzyme was assessed by spectrophotometric bioassay using Neostigmine Methyl Sulfate as a standard acetycholinesterase inhibitor. The surface modification was studied through field emission SEM, Fourier transform IR spectroscopy, energy-dispersive X-ray spectroscopy, cathode luminescence and X-ray photoelectron spectroscopy analysis, photoluminescence measurement and spectrophotometric bioassay. The porous silicon-immobilized enzyme not only yielded greater enzyme stability, but also significantly improved the native photoluminescence at room temperature of the bare porous silicon architecture. The results indicated the promising catalytic behaviour of immobilized enzyme compared with that of its free counterpart, with a greater stability, and that it aided reusability and easy separation from the reaction mixture. The porous silicon-immobilized enzyme was found to retain 50% of its activity, promising thermal stability up to 90°C, reusability for up to three cycles, pH stability over a broad pH of 4–9 and a shelf-life of 44 days, with an optimal hydrolytic response towards acetylthiocholine iodide at variable drug concentrations. On the basis of these findings, it was believed that the porous silicon-immobilized enzyme could be exploited as a reusable biocatalyst and for screening of acetylcholinesterase inhibitors from crude plant extracts and synthesized organic compounds. Moreover, the immobilized enzyme could offer a great deal as a viable biocatalyst in bioprocessing for the chemical and pharmaceutical industries, and bioremediation to enhance productivity and robustness.
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Photoluminescent sensor for acetylcholinesterase inhibitor determination
Journal of materials chemistry. B, 2014Co-Authors: Muhammad Saleem, Luke P. Lee, Ki Hwan LeeAbstract:An acetylcholinesterase immobilized p-type porous silicon material for sensing acetylcholinesterase inhibitors was demonstrated. The enzyme immobilized photoluminescence surface upon incubation with standard acetylcholinesterase inhibitors (Neostigmine Methyl Sulfate and tacrine) for 30 minutes at 37 °C triggers the photoluminescence with up to a 3 fold enhancement in the intensity with a hypsochromic shift of 3 nm. The dramatic change in photoluminescence of the enzyme immobilized surface upon reaction with the enzyme inhibitor can be used as a tool for the detection of acetylcholinesterase inhibitors by utilizing the subsequent photoluminescence response after the incubation with the corresponding inhibitor drug.
Debomoy K Lahiri - One of the best experts on this subject based on the ideXlab platform.
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long acting anticholinesterases for myasthenia gravis synthesis and activities of quaternary phenylcarbamates of Neostigmine pyridostigmine and physostigmine
Bioorganic & Medicinal Chemistry, 2010Co-Authors: Qian Sheng Yu, Harold W Holloway, Debomoy K Lahiri, Arnold Brossi, Nigel H GreigAbstract:The N-monophenylcarbamate analogues of Neostigmine Methyl Sulfate (6) and pyridostigmine bromide (8) together with their precursors (5), (7), and the N(1)-Methylammonium analogues of (−)-phenserine (12), (−)-tolserine (14), (−)-cymserine (16) and (−)-phenethylcymserine (18) were synthesized to produce long-acting peripheral inhibitors of acetylcholinesterase or butyrylcholinesterase. Evaluation of their cholinesterase inhibition against human enzyme ex vivo demonstrated that, whereas compounds 5–8 possessed only marginal activity, 12, 14, 16 and 18 proved to be potent anticholinesterases. An extended duration of cholinesterase inhibition was determined in rodent, making them of potential interest as long-acting agents for myasthenia gravis.