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Molecules 2018, 23(2), 496; https://doi.org/10.3390/molecules23020496

In Silico-Based Repositioning of Phosphinothricin as a Novel Technetium-99m Imaging Probe with Potential Anti-Cancer Activity

1
Radioactive Isotopes and Generator Department, Hot Labs Center, Atomic Energy Authority, Cairo 13759, Egypt
2
Pharmaceutical Chemistry Department, Faculty of Pharmacy, October University of Modern Sciences and Arts (MSA), Giza 12111, Egypt
3
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo 11795, Egypt
4
College of Clinical Pharmacy, King Faisal University, Al-Hasaa 31982, Kingdom of Saudi Arabia
5
Labeled Compounds Department, Hot Labs Center, Atomic Energy Authority, Cairo 13759, Egypt
6
Department of Pharmacognosy, Faculty of Pharmacy, University of Zagazig, Zagazig 44519, Egypt
*
Author to whom correspondence should be addressed.
Received: 19 January 2018 / Revised: 8 February 2018 / Accepted: 16 February 2018 / Published: 23 February 2018
(This article belongs to the Special Issue Molecular Imaging and Treatment Monitoring of Cancer)
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Abstract

l-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. View Full-Text
Keywords: in-silico; repositioning; technetium-99m; cancer imaging; phosphinothricin; molecular docking in-silico; repositioning; technetium-99m; cancer imaging; phosphinothricin; molecular docking
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Sakr, T.M.; Khedr, M.A.; Rashed, H.M.; Mohamed, M.E. In Silico-Based Repositioning of Phosphinothricin as a Novel Technetium-99m Imaging Probe with Potential Anti-Cancer Activity. Molecules 2018, 23, 496.

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