Bisphosphonate sequestering agents. Synthesis and preliminary evaluation for in vitro and in vivo uranium(VI) chelation

Sawicki, Marcin; Lecerclé, Delphine; Grillon, G.; Gall, B. Le; Sérandour, Anne-Laure; Poncy, Jean-Luc; Bailly, Théodorine; Burgada, R.; Lecouvey, Marc; Challeix, Vincent; Leydier, Antoine; Pellet‐Rostaing, Stéphane; Ansoborlo, É.; Taran, Frédéric

doi:10.1016/j.ejmech.2008.01.018

Cited by 45 publications

(26 citation statements)

References 42 publications

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“…Another study also shows that gencitabine‐bisphosphonate are mainly (67%) retained in the bone 8 h after administration. This can be used to specifically target bone metastasis [Sawicki et al, 2008].…”

Section: Bisphosphonates As Bone‐seeking Agentsmentioning

confidence: 99%

Bisphosphonates, specific inhibitors of osteoclast function and a class of drugs for osteoporosis therapy

Chau

Wang

et al. 2011

J of Cellular Biochemistry

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Osteoporosis is a result of the disruption of bone homeostasis that is carried out by bone-forming osteoblasts and bone-degrading osteoclasts. The most common treatment of osteoporosis is N-containing bisphosphonates, a class of non-hydrolyzable pyrophosphate analogs. They have strong affinity to Ca(2+) of hydroxyapatite with high specificity and can only be liberated from the bone in an acidic environment. These properties bestow them unique pharmacokinetic features including specific and strong retention at bone resorption surface, uptaken specifically by osteoclasts, quick excretion of non-retained free bisphosphonates, long half-life, and recyclability. Such properties underlie the drugs' high efficacy, minor side effects, and intermittent dosing regimens. Further studies show that bisphosphonates inhibit farnesyl pyrophosphate synthase, a critical enzyme required for synthesis of isoprenyl and geranylgeranyl, and inhibit prenylation and geranylgeranylation of small G-proteins such as Rac and Rho. This leads to defective actin ring formation at the sealed zone, a subcellular structure essential for bone resorption, and a decrease in bone resorption. Bisphosphonates are also used to treat Paget's disease of bone, osteolytic bone metastases, and hypercalcemia. Moreover, these properties also make N-BPs a good candidate as a bone-seeking agent. Here we update our understanding of this remarkable class of anti-resorption drugs.

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Section: Bisphosphonates As Bone‐seeking Agentsmentioning

confidence: 99%

Bisphosphonates, specific inhibitors of osteoclast function and a class of drugs for osteoporosis therapy

Chau

Wang

et al. 2011

J of Cellular Biochemistry

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“…1 Synthesis of 1,3,5-benzene tricarboxylic acid tris-N-(2-aminoethyl) amide 1,3,5-Benzene tricarboxylic acid tris-N-(2-aminoethyl) amide (BTATAA) was attained by amination reaction of EDA reported elsewhere. 25,[28][29][30][31][32] Flesh EDA of 20 mL (0.3 mol) was added into a 100-mL three flask, and then 0.63 g (2.5 mmol) TMBT dissolved in 40 mL methanol in advance was slowly added into the solution by a constant pressure funnel. The mixture was stirred under nitrogen atmosphere at 0 C for 30 min, and then at 25 C for 24 h. Excess EDA was removed by rotary evaporation, and then, the resultant crude product was dissolved in methanol/toluene (1/10 by volume) mixed solvents and re-evaporated to remove the residual EDA.…”

Section: Synthesis Of Trimethyl Benzene-135-tricarboxylatementioning

confidence: 99%

Self‐assembly micelles from novel tri‐armed star C₃‐(PS‐b‐PNIPAM) block copolymers for anticancer drug release

Zhang

et al. 2014

AIChE Journal

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Novel tri-armed star polystyrene-block-poly(N-isopropylacrylamide) block copolymers with trimesic acid as central molecules were synthesized by successive two-step atom transfer radical polymerization, and confirmed by Fouriertransform infrared spectra, 1 H nuclear magnetic resonance, and laser light scattering gel chromatography system. The copolymers could self-assemble into spherical core-shell micelles in aqueous media independent on drug loading. Physicochemical properties of the blank and drug-loaded micelles were examined by surface tension, fluorescence spectroscopy, UV-vis, transmission electron microscope, and dynamic light scattering measurements. The copolymer micelles exhibited thermo-triggered phase transition, with low critical solution temperature of 33.7 and 34.6 C, varying with copolymer compositions. The critical aggregate concentrations were 11.62 and 47.61 mg L 21 , and hydrodynamic diameters from 200 to 220 nm. Water-insoluble 10-hydroxycamptothecine was encapsulated into the micelle aggregates to investigate the change in the resulting physicochemical parameters, thermo-triggered in vitro drug release, and the applicability as drug targeting release carriers. MTT assays were carried out to uncover cytotoxicity of the newly developed micelle-based drug formulations. V C 2014 American Institute of Chemical Engineers AIChE J, 61: [35][36][37][38][39][40][41][42][43][44][45] 2015

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“…Importantly, L1 has also been found to function as a free radical scavenger to prevent radiation-induced injury (8,9). Moreover, other chelating agents such as catechol-3,6-bis(methyleiminodiacetic acid) (10), Calixarenes (11), inositol hexaphosphate (12), and new uranophiles of dipodal bis-sulfocatecholamide (13) and di(or tri)podal bisphosphonates (14,15) have also been studied as potential antidotes for U decorporation. Interestingly, ethane-1-hydroxy-1,1-bisphosphonate, a drug for osteoporosis with chelating properties, has been examined in U-contaminated animals, and results have revealed the capability of the drug to remove U from New Chelator For Uranium Internal Decontamination 293 the animal body (16).…”

Section: Introductionmentioning

confidence: 98%

1-(2-Hydroxyethoxy)Methyl-2-Methyl-3-Hydroxyl-4-Pyridinone: ATargeted, Bifunctional Chelating Agent for Potential Uranic Detoxification in the Kidney

2011

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The only proposed treatment for uranium (U) internal decontamination is chelation therapy, and so far, there is no effective chelating drug available for this purpose. A modified iron chelator of deferiprone (L1) has been investigated for its chemical and pharmacological properties as a new U chelating agent. The results have demonstrated that the chelator, 1-(2-hydroxyethoxy)methyl-2-methyl-3-hydroxyl-4-pyridinone (HEML1), has the ability to chelate uranyl ion, forming a stable complex with 2:1 (chelator/U) stoichiometry. The chelator, HEML1, does not pose any adverse effects on cultured human kidney cells, and shows the capability of protecting the cells against U-associated cytotoxicity and hydrogen peroxide-induced free radical damage. Moreover, because of the hydrophilic property of both HEML1 and its U-complex, the chelator has the potential to target the kidneys where the U prefer to deposit, and to leave the organ after complexing U. These results suggest that HEML1 may be able to serve as a bifunctional therapeutic for internal radionuclide decontamination.

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Bisphosphonate sequestering agents. Synthesis and preliminary evaluation for in vitro and in vivo uranium(VI) chelation

Cited by 45 publications

References 42 publications

Bisphosphonates, specific inhibitors of osteoclast function and a class of drugs for osteoporosis therapy

Bisphosphonates, specific inhibitors of osteoclast function and a class of drugs for osteoporosis therapy

Self‐assembly micelles from novel tri‐armed star C₃‐(PS‐b‐PNIPAM) block copolymers for anticancer drug release

1-(2-Hydroxyethoxy)Methyl-2-Methyl-3-Hydroxyl-4-Pyridinone: ATargeted, Bifunctional Chelating Agent for Potential Uranic Detoxification in the Kidney

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Bisphosphonate sequestering agents. Synthesis and preliminary evaluation for in vitro and in vivo uranium(VI) chelation

Cited by 45 publications

References 42 publications

Bisphosphonates, specific inhibitors of osteoclast function and a class of drugs for osteoporosis therapy

Bisphosphonates, specific inhibitors of osteoclast function and a class of drugs for osteoporosis therapy

Self‐assembly micelles from novel tri‐armed star C3‐(PS‐b‐PNIPAM) block copolymers for anticancer drug release

1-(2-Hydroxyethoxy)Methyl-2-Methyl-3-Hydroxyl-4-Pyridinone: ATargeted, Bifunctional Chelating Agent for Potential Uranic Detoxification in the Kidney

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Self‐assembly micelles from novel tri‐armed star C₃‐(PS‐b‐PNIPAM) block copolymers for anticancer drug release