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      Molecular docking studies of coumarin hybrids as potential acetylcholinesterase, butyrylcholinesterase, monoamine oxidase A/B and β-amyloid inhibitors for Alzheimer’s disease

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          Abstract

          Coumarins are the phytochemicals, which belong to the family of benzopyrone, that display interesting pharmacological properties. Several natural, synthetic and semisynthetic coumarin derivatives have been discovered in decades for their applicability as lead structures as drugs. Coumarin based conjugates have been described as potential AChE, BuChE, MAO and β-amyloid inhibitors. Therefore, the objective of this review is to focus on the construction of these pharmacologically important coumarin analogues with anti-Alzheimer’s activities, highlight their docking studies and structure–activity relationships based on their substitution pattern with respect to the selected positions on the chromen ring by emphasising on the research reports conducted in between year 1968 to 2017.

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          Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein.

          The three-dimensional structure of acetylcholinesterase from Torpedo californica electric organ has been determined by x-ray analysis to 2.8 angstrom resolution. The form crystallized is the glycolipid-anchored homodimer that was purified subsequent to solubilization with a bacterial phosphatidylinositol-specific phospholipase C. The enzyme monomer is an alpha/beta protein that contains 537 amino acids. It consists of a 12-stranded mixed beta sheet surrounded by 14 alpha helices and bears a striking resemblance to several hydrolase structures including dienelactone hydrolase, serine carboxypeptidase-II, three neutral lipases, and haloalkane dehalogenase. The active site is unusual because it contains Glu, not Asp, in the Ser-His-acid catalytic triad and because the relation of the triad to the rest of the protein approximates a mirror image of that seen in the serine proteases. Furthermore, the active site lies near the bottom of a deep and narrow gorge that reaches halfway into the protein. Modeling of acetylcholine binding to the enzyme suggests that the quaternary ammonium ion is bound not to a negatively charged "anionic" site, but rather to some of the 14 aromatic residues that line the gorge.
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            Acetylcholinesterase: enzyme structure, reaction dynamics, and virtual transition states

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              Monoamine oxidase: isoforms and inhibitors in Parkinson's disease and depressive illness.

              A few years after the foundation of the British Pharmacological Society, monoamine oxidase (MAO) was recognized as an enzyme of crucial interest to pharmacologists because it catalyzed the major inactivation pathway for the catecholamine neurotransmitters, noradrenaline, adrenaline and dopamine (and, later, 5-hydroxytryptamine, as well). Within the next decade, the therapeutic value of inhibitors of MAO in the treatment of depressive illness was established. Although this first clinical use exposed serious side effects, pharmacological interest in, and investigation of, MAO continued, resulting in the characterization of two isoforms, MAO-A and -B, and isoform-selective inhibitors. Selective inhibitors of MAO-B have found a therapeutic role in the treatment of Parkinson's disease and further developments have provided reversible inhibitors of MAO-A, which offer antidepressant activity without the serious side effects of the earlier inhibitors. Clinical observation and subsequent pharmacological analysis have also generated the concept of neuroprotection, reflecting the possibility of slowing, halting and maybe reversing, neurodegeneration in Parkinson's or Alzheimer's diseases. Increased levels of oxidative stress in the brain may be critical for the initiation and progress of neurodegeneration and selective inhibition of brain MAO could contribute importantly to lowering such stress. There are complex interactions between free iron levels in brain and MAO, which may have practical outcomes for depressive disorders. These aspects of MAO and its inhibition and some indication of how this important area of pharmacology and therapeutics might develop in the future are summarized in this review.
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                Author and article information

                Contributors
                shaheenchem@gmail.com
                Journal
                Chem Cent J
                Chem Cent J
                Chemistry Central Journal
                Springer International Publishing (Cham )
                1752-153X
                4 December 2018
                4 December 2018
                2018
                : 12
                : 128
                Affiliations
                [1 ]ISNI 0000 0001 2294 3534, GRID grid.11875.3a, School of Industrial Technology, , Universiti Sains Malaysia, ; 11800 Penang, Malaysia
                [2 ]ISNI 0000 0001 0417 0814, GRID grid.265727.3, Industrial Chemistry Programme, Faculty of Science and Natural Resources, , Universiti Malaysia Sabah, ; 88400 Kota Kinabalu, Sabah Malaysia
                [3 ]ISNI 0000 0001 2294 3534, GRID grid.11875.3a, School of Chemical Sciences, , Universiti Sains Malaysia, ; 11800 Penang, Malaysia
                Article
                497
                10.1186/s13065-018-0497-z
                6768047
                30515636
                f42cbcde-b899-4c0a-bbc1-d2ded7c39125
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 26 July 2018
                : 21 November 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100006242, Universiti Malaysia Sabah;
                Award ID: SLB0052-SG-2013
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                Chemistry
                coumarin,neurodegenerative disorder,alzheimer’s disease,acetylcholinesterase,butyrylcholinesterase,monoamine oxidase

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