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

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Tamer M SakrMaged E Mohamed

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 ...Continue Reading

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Citations

May 23, 2019·International Journal of Molecular Medicine·Octavian Tudorel OlaruOana Cristina Seremet
Oct 2, 2019·Cancer Letters·José M MatésJavier Márquez
May 5, 2020·Current Medicinal Chemistry·Janke KleynhansThomas Ebenhan
Sep 29, 2021·Journal of Labelled Compounds & Radiopharmaceuticals·Moamen M SolimanHassan A Abd El-Rehim

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Methods Mentioned

BETA
X-ray

Software Mentioned

MOE
MMFF94x
Molecular Operating Environment MOE

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