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      Marine Natural Products with P-Glycoprotein Inhibitor Properties

      review-article
      Author(s): 1 , 2 , 1 , *
      Publication date (Electronic):
      Journal: Marine Drugs
      Publisher: MDPI
      Keywords: P-glycoprotein, marine natural products, multidrug resistance

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          Abstract

          P-glycoprotein (P-gp) is a protein belonging to the ATP-binding cassette (ABC) transporters superfamily that has clinical relevance due to its role in drug metabolism and multi-drug resistance (MDR) in several human pathogens and diseases. P-gp is a major cause of drug resistance in cancer, parasitic diseases, epilepsy and other disorders. This review article aims to summarize the research findings on the marine natural products with P-glycoprotein inhibitor properties. Natural compounds that modulate P-gp offer great possibilities for semi-synthetic modification to create new drugs and are valuable research tools to understand the function of complex ABC transporters.

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          Most cited references118

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          Biochemical, cellular, and pharmacological aspects of the multidrug transporter.

          S Ambudkar, S. Dey, C A Hrycyna … (1999)
          Considerable evidence has accumulated indicating that the multidrug transporter or P-glycoprotein plays a role in the development of simultaneous resistance to multiple cytotoxic drugs in cancer cells. In recent years, various approaches such as mutational analyses and biochemical and pharmacological characterization have yielded significant information about the relationship of structure and function of P-glycoprotein. However, there is still considerable controversy about the mechanism of action of this efflux pump and its function in normal cells. This review summarizes current research on the structure-function analysis of P-glycoprotein, its mechanism of action, and facts and speculations about its normal physiological role.
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            Marine natural products.

            John Blunt, Brent Copp, Robert A Keyzers … (2013)
            This review covers the literature published in 2011 for marine natural products, with 870 citations (558 for the period January to December 2011) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1152 for 2011), together with the relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.
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              The ATP switch model for ABC transporters.

              Gloria Higgins, K Linton (2004)
              ABC transporters mediate active translocation of a diverse range of molecules across all cell membranes. They comprise two nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs). Recent biochemical, structural and genetic studies have led to the ATP-switch model in which ATP binding and ATP hydrolysis, respectively, induce formation and dissociation of an NBD dimer. This provides an exquisitely regulated switch that induces conformational changes in the TMDs to mediate membrane transport.
              Article 0 comments Cited 154 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Mar Drugs
                Journal ID (iso-abbrev): Mar Drugs
                Journal ID (publisher-id): marinedrugs
                Title: Marine Drugs
                Publisher: MDPI
                ISSN (Electronic): 1660-3397
                Publication date (Electronic): 22 January 2014
                Publication date Collection: January 2014
                Volume: 12
                Issue: 1
                Pages: 525-546
                Affiliations
                [1 ]Center for Drug Discovery and Biodiversity, Institute for Scientific Research and Technology Services (INDICASAT), Clayton, City of Knowledge, P.O. Box 0843-01103, Panama; E-Mail: dioxelis.lopez@ 123456indicasat.org.pa
                [2 ]Department of Biotechnology, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur 522510, India
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: smartinez@ 123456indicasat.org.pa ; Tel.: +507-517-0700; Fax: +507-507-0020.
                Article
                Publisher ID: marinedrugs-12-00525
                DOI: 10.3390/md12010525
                PMC ID: 3917285
                PubMed ID: 24451193
                SO-VID: 94faa72f-4f08-4271-aa43-608d06daeef2
                Copyright © © 2014 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 22 November 2013
                Date revision received : 06 January 2014
                Date accepted : 07 January 2014
                Categories
                Subject: Review

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: marine natural products,multidrug resistance,p-glycoprotein
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: marine natural products, multidrug resistance, p-glycoprotein

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