In silico-based repositioning of phosphinothricin as a novel technetium-99m imaging probe with potential anti-cancer activity

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dc.AffiliationOctober University for modern sciences and Arts (MSA)
dc.contributor.authorSakr T.M.
dc.contributor.authorKhedr M.A.
dc.contributor.authorRashed H.M.
dc.contributor.authorMohamed M.E.
dc.contributor.otherRadioactive Isotopes and Generator Department
dc.contributor.otherHot Labs Center
dc.contributor.otherAtomic Energy Authority
dc.contributor.otherCairo
dc.contributor.other13759
dc.contributor.otherEgypt; Pharmaceutical Chemistry Department
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherOctober University of Modern Sciences and Arts (MSA)
dc.contributor.otherGiza
dc.contributor.other12111
dc.contributor.otherEgypt; Department of Pharmaceutical Chemistry
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherHelwan University
dc.contributor.otherEin Helwan
dc.contributor.otherCairo
dc.contributor.other11795
dc.contributor.otherEgypt; College of Clinical Pharmacy
dc.contributor.otherKing Faisal University
dc.contributor.otherAl-Hasaa
dc.contributor.other31982
dc.contributor.otherSaudi Arabia; Labeled Compounds Department
dc.contributor.otherHot Labs Center
dc.contributor.otherAtomic Energy Authority
dc.contributor.otherCairo
dc.contributor.other13759
dc.contributor.otherEgypt; Department of Pharmacognosy
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherUniversity of Zagazig
dc.contributor.otherZagazig
dc.contributor.other44519
dc.contributor.otherEgypt
dc.date.accessioned2020-01-09T20:40:54Z
dc.date.available2020-01-09T20:40:54Z
dc.date.issued2018
dc.descriptionScopus
dc.descriptionMSA Google Scholar
dc.description.abstractL-Phosphinothricin (glufosinate or 2-amino-4-((hydroxy(methyl) phosphinyl) butyric acid ammonium salt (AHPB)), which is a structural analog of glutamate, is a recognized herbicide that acts on weeds through inhibition of glutamine synthetase. Due to the structural similarity between phosphinothricin and some bisphosphonates (BPs), this study focuses on investigating the possibility of repurposing phosphinothricin as a bisphosphonate analogue, particularly in two medicine-related activities: image probing and as an anti-cancer drug. As BP is a competitive inhibitor of human farnesyl pyrophosphate synthase (HFPPS), in silico molecular docking and dynamic simulations studies were established to evaluate the binding and stability of phosphinothricin with HFPPS, while the results showed good binding and stability in the active site of the enzyme in relation to alendronate. For the purpose of inspecting bone-tissue accumulation of phosphinothricin, a technetium (99mTc)�phosphinothricin complex was developed and its stability and tissue distribution were scrutinized. The radioactive complex showed rapid, high and sustained uptake into bone tissues. Finally, the cytotoxic activity of phosphinothricin was tested against breast and lung cancer cells, with the results indicating cytotoxic activity in relation to alendronate. All the above results provide support for the use of phosphinothricin as a potential anti-cancer drug and of its technetium complex as an imaging probe. � 2018 by the authors.en_US
dc.description.urihttps://www.scimagojr.com/journalsearch.php?q=26370&tip=sid&clean=0
dc.identifier.doihttps://doi.org/10.3390/molecules23020496
dc.identifier.doiPubMed ID 29473879
dc.identifier.issn14203049
dc.identifier.otherhttps://doi.org/10.3390/molecules23020496
dc.identifier.otherPubMed ID 29473879
dc.identifier.urihttps://t.ly/vejRA
dc.language.isoEnglishen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofseriesMolecules
dc.relation.ispartofseries23
dc.subjectOctober University for Modern Sciences and Arts
dc.subjectجامعة أكتوبر للعلوم الحديثة والآداب
dc.subjectUniversity of Modern Sciences and Arts
dc.subjectMSA University
dc.subjectCancer imagingen_US
dc.subjectIn-silicoen_US
dc.subjectMolecular dockingen_US
dc.subjectPhosphinothricinen_US
dc.subjectRepositioningen_US
dc.subjectTechnetium-99men_US
dc.subjectalendronic aciden_US
dc.subjectaminobutyric acid derivativeen_US
dc.subjectantineoplastic agenten_US
dc.subjectphosphinothricinen_US
dc.subjectradiopharmaceutical agenten_US
dc.subjecttechnetiumen_US
dc.subjectTechnetium-99en_US
dc.subjectanimalen_US
dc.subjectbinding siteen_US
dc.subjectcell proliferationen_US
dc.subjectchemical structureen_US
dc.subjectchemistryen_US
dc.subjectdiagnostic imagingen_US
dc.subjectdrug effecten_US
dc.subjectdrug repositioningen_US
dc.subjectdrug stabilityen_US
dc.subjecthumanen_US
dc.subjectmolecular dockingen_US
dc.subjectmolecular dynamicsen_US
dc.subjectmouseen_US
dc.subjectpHen_US
dc.subjectstructure activity relationen_US
dc.subjecttissue distributionen_US
dc.subjecttumor cell lineen_US
dc.subjectAlendronateen_US
dc.subjectAminobutyratesen_US
dc.subjectAnimalsen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectBinding Sitesen_US
dc.subjectCell Line, Tumoren_US
dc.subjectCell Proliferationen_US
dc.subjectDiagnostic Imagingen_US
dc.subjectDrug Repositioningen_US
dc.subjectDrug Stabilityen_US
dc.subjectHumansen_US
dc.subjectHydrogen-Ion Concentrationen_US
dc.subjectMiceen_US
dc.subjectMolecular Docking Simulationen_US
dc.subjectMolecular Dynamics Simulationen_US
dc.subjectMolecular Structureen_US
dc.subjectRadiopharmaceuticalsen_US
dc.subjectStructure-Activity Relationshipen_US
dc.subjectTechnetiumen_US
dc.subjectTissue Distributionen_US
dc.titleIn silico-based repositioning of phosphinothricin as a novel technetium-99m imaging probe with potential anti-cancer activityen_US
dc.typeArticleen_US
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