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.
Highlights
Bone-seekers are a group of complexes of radioisotopes that tend to accumulate in bones when they are introduced into the body
Technetium-99m is one of the well-known rare earth radioisotopes used in radioisotopes used in bone-seeker complexes
Phosphinothricin was repurposed as an anti-cancer drug because of its structural similarity to alendronate
Summary
Bone-seekers are a group of complexes of radioisotopes that tend to accumulate in bones when they are introduced into the body. The mechanisms involved in the uptake of these complexes into bone tissue are still unclear and under investigation. These mechanisms can involve simple chemisorption onto bone minerals. Technetium-99m is one of the well-known rare earth compartments of bone [2]. Technetium-99m is one of the well-known rare earth radioisotopes used in radioisotopes used in bone-seeker complexes. This compound noticeably reduces patients’ radiation bone-seeker complexes. This compound noticeably reduces patients’ radiation exposure and shows exposure and shows more favorable physical decay characteristics, which leads to increased more favorable physical decay characteristics, which leads to increased sensitivity and resolution and sensitivity and resolution and improved diagnostic efficacy [3]
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