Blog
About

  • Record: found
  • Abstract: found
  • Article: found
Is Open Access

Profiling donepezil template into multipotent hybrids with antioxidant properties

Read this article at

Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      Alzheimer’s disease is debilitating neurodegenerative disorder in the elderly. Current therapy relies on administration of acetylcholinesterase inhibitors (AChEIs) -donepezil, rivastigmine, galantamine, and N-methyl- d-aspartate receptor antagonist memantine. However, their therapeutic effect is only short-term and stabilizes cognitive functions for up to 2 years. Given this drawback together with other pathological hallmarks of the disease taken into consideration, novel approaches have recently emerged to better cope with AD onset or its progression. One such strategy implies broadening the biological profile of AChEIs into so-called multi-target directed ligands (MTDLs). In this review article, we made comprehensive literature survey emphasising on donepezil template which was structurally converted into plethora of MTLDs preserving anti-cholinesterase effect and, at the same time, escalating the anti-oxidant potential, which was reported as a crucial role in the pathogenesis of the Alzheimer’s disease.

      Abstract

      Related collections

      Most cited references 168

      • Record: found
      • Abstract: found
      • Article: not found

      The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": the FRAP assay.

      A simple, automated test measuring the ferric reducing ability of plasma, the FRAP assay, is presented as a novel method for assessing "antioxidant power." Ferric to ferrous ion reduction at low pH causes a colored ferrous-tripyridyltriazine complex to form. FRAP values are obtained by comparing the absorbance change at 593 nm in test reaction mixtures with those containing ferrous ions in known concentration. Absorbance changes are linear over a wide concentration range with antioxidant mixtures, including plasma, and with solutions containing one antioxidant in purified form. There is no apparent interaction between antioxidants. Measured stoichiometric factors of Trolox, alpha-tocopherol, ascorbic acid, and uric acid are all 2.0; that of bilirubin is 4.0. Activity of albumin is very low. Within- and between-run CVs are <1.0 and <3.0%, respectively, at 100-1000 micromol/liter. FRAP values of fresh plasma of healthy Chinese adults: 612-1634 micromol/liter (mean, 1017; SD, 206; n = 141). The FRAP assay is inexpensive, reagents are simple to prepare, results are highly reproducible, and the procedure is straightforward and speedy. The FRAP assay offers a putative index of antioxidant, or reducing, potential of biological fluids within the technological reach of every laboratory and researcher interested in oxidative stress and its effects.
        Bookmark
        • Record: found
        • Abstract: found
        • Article: not found

        Antioxidant activity applying an improved ABTS radical cation decolorization assay.

        A method for the screening of antioxidant activity is reported as a decolorization assay applicable to both lipophilic and hydrophilic antioxidants, including flavonoids, hydroxycinnamates, carotenoids, and plasma antioxidants. The pre-formed radical monocation of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS*+) is generated by oxidation of ABTS with potassium persulfate and is reduced in the presence of such hydrogen-donating antioxidants. The influences of both the concentration of antioxidant and duration of reaction on the inhibition of the radical cation absorption are taken into account when determining the antioxidant activity. This assay clearly improves the original TEAC assay (the ferryl myoglobin/ABTS assay) for the determination of antioxidant activity in a number of ways. First, the chemistry involves the direct generation of the ABTS radical monocation with no involvement of an intermediary radical. Second, it is a decolorization assay; thus the radical cation is pre-formed prior to addition of antioxidant test systems, rather than the generation of the radical taking place continually in the presence of the antioxidant. Hence the results obtained with the improved system may not always be directly comparable with those obtained using the original TEAC assay. Third, it is applicable to both aqueous and lipophilic systems.
          Bookmark
          • Record: found
          • Abstract: found
          • Article: not found

          The chemistry behind antioxidant capacity assays.

          This review summarizes the multifaceted aspects of antioxidants and the basic kinetic models of inhibited autoxidation and analyzes the chemical principles of antioxidant capacity assays. Depending upon the reactions involved, these assays can roughly be classified into two types: assays based on hydrogen atom transfer (HAT) reactions and assays based on electron transfer (ET). The majority of HAT-based assays apply a competitive reaction scheme, in which antioxidant and substrate compete for thermally generated peroxyl radicals through the decomposition of azo compounds. These assays include inhibition of induced low-density lipoprotein autoxidation, oxygen radical absorbance capacity (ORAC), total radical trapping antioxidant parameter (TRAP), and crocin bleaching assays. ET-based assays measure the capacity of an antioxidant in the reduction of an oxidant, which changes color when reduced. The degree of color change is correlated with the sample's antioxidant concentrations. ET-based assays include the total phenols assay by Folin-Ciocalteu reagent (FCR), Trolox equivalence antioxidant capacity (TEAC), ferric ion reducing antioxidant power (FRAP), "total antioxidant potential" assay using a Cu(II) complex as an oxidant, and DPPH. In addition, other assays intended to measure a sample's scavenging capacity of biologically relevant oxidants such as singlet oxygen, superoxide anion, peroxynitrite, and hydroxyl radical are also summarized. On the basis of this analysis, it is suggested that the total phenols assay by FCR be used to quantify an antioxidant's reducing capacity and the ORAC assay to quantify peroxyl radical scavenging capacity. To comprehensively study different aspects of antioxidants, validated and specific assays are needed in addition to these two commonly accepted assays.
            Bookmark

            Author and article information

            Affiliations
            [a ] Biomedical Research Centre, University Hospital Hradec Kralove , Hradec Kralove, Czech Republic;
            [b ] National Institute of Mental Health , Klecany, Czech Republic;
            [c ] Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences , Hradec Kralove, Czech Republic;
            [d ] Department of Chemistry, University of Hradec Kralove , Hradec Kralove, Czech Republic
            Author notes
            CONTACT Kamil Kuca kamil.kuca@ 123456fnhk.cz Biomedical Research Centre, University Hospital Hradec Kralove , Sokolska 581, 500 05Hradec Kralove, Czech Republic
            Jan Korabecny korabecny.jan@ 123456gmail.com Biomedical Research Centre, University Hospital Hradec Kralove , Sokolska 581, 500 05Hradec Kralove, Czech Republic
            Journal
            J Enzyme Inhib Med Chem
            J Enzyme Inhib Med Chem
            IENZ
            ienz20
            Journal of Enzyme Inhibition and Medicinal Chemistry
            Taylor & Francis
            1475-6366
            1475-6374
            2018
            13 March 2018
            : 33
            : 1
            : 583-606
            29529892
            6009928
            10.1080/14756366.2018.1443326
            1443326
            © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

            This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

            Counts
            Pages: 24, Words: 15900
            Product
            Funding
            Funded by: Ministry of Health of the Czech Republic 10.13039/501100003243
            Award ID: 15–30954A
            Funded by: National Institute of Mental Health 10.13039/100000025
            The work was supported by the grant of Ministry of Health of the Czech Republic [grant No. 15–30954A] by the University of Defense and UHK (Long Term Development Plan), by National Institute of Mental Health (NIMH-CZ) project No. LO1611 with a financial support from the MEYS under the NPU I program.
            Categories
            Review Article

            Comments

            Comment on this article