Sakr T.M.Khedr M.A.Rashed H.M.Mohamed M.E.Radioactive Isotopes and Generator DepartmentHot Labs CenterAtomic Energy AuthorityCairo13759Egypt; Pharmaceutical Chemistry DepartmentFaculty of PharmacyOctober University of Modern Sciences and Arts (MSA)Giza12111Egypt; Department of Pharmaceutical ChemistryFaculty of PharmacyHelwan UniversityEin HelwanCairo11795Egypt; College of Clinical PharmacyKing Faisal UniversityAl-Hasaa31982Saudi Arabia; Labeled Compounds DepartmentHot Labs CenterAtomic Energy AuthorityCairo13759Egypt; Department of PharmacognosyFaculty of PharmacyUniversity of ZagazigZagazig44519Egypt2020-01-092020-01-09201814203049https://doi.org/10.3390/molecules23020496PubMed ID 29473879https://t.ly/vejRAScopusMSA Google ScholarL-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.EnglishOctober University for Modern Sciences and Artsجامعة أكتوبر للعلوم الحديثة والآدابUniversity of Modern Sciences and ArtsMSA UniversityCancer imagingIn-silicoMolecular dockingPhosphinothricinRepositioningTechnetium-99malendronic acidaminobutyric acid derivativeantineoplastic agentphosphinothricinradiopharmaceutical agenttechnetiumTechnetium-99animalbinding sitecell proliferationchemical structurechemistrydiagnostic imagingdrug effectdrug repositioningdrug stabilityhumanmolecular dockingmolecular dynamicsmousepHstructure activity relationtissue distributiontumor cell lineAlendronateAminobutyratesAnimalsAntineoplastic AgentsBinding SitesCell Line, TumorCell ProliferationDiagnostic ImagingDrug RepositioningDrug StabilityHumansHydrogen-Ion ConcentrationMiceMolecular Docking SimulationMolecular Dynamics SimulationMolecular StructureRadiopharmaceuticalsStructure-Activity RelationshipTechnetiumTissue DistributionArticlehttps://doi.org/10.3390/molecules23020496PubMed ID 29473879