Search results for "phosphonates"
showing 10 items of 210 documents
Mevalonate pathway inhibitors affect anticancer drug-induced cell death and DNA damage response of human sarcoma cells
2011
Lovastatin (Lov), bisphosphonates (BP) and metformin (Met) are widely used drugs, having in common that they interfere with the mevalonate pathway (MP). The MP generates isoprene moieties required for the function of regulatory GTPases controlling cell proliferation and survival. Here, we addressed the question whether MP inhibitors interfere with the anti-tumor efficacy of anticancer drugs. We comparatively analyzed the effect of equitoxic doses of Lov, BP and Met on cell viability, cell cycle progression, apoptosis and DNA damage response (DDR) of human osteo- and fibrosarcoma cells exposed to doxorubicin or cisplatin. We found that Lov, BP and Met modulated the anticancer drug sensitivit…
Systematic study of the physicochemical properties of a homologous series of aminobisphosphonates
2012
ABSTRACT: Aminobisphosphonates, e.g., alendronate and neridronate, are a well known class of molecules used as drugs for various bone diseases. Although these molecules have been available for decades, a detailed understanding of their most important physicochemical properties under comparable conditions is lacking. In this study, ten aminobisphosphonates, H2N(CH2)nC(OH)[P(O)(OH)2]2, in which n = 2-5, 7-11 and 15 have been synthesized. Their aqueous solubility as a function of temperature and pH, pKa-values, thermal stability, IR absorptions, and NMR spectral data for both liquid (1H, 13C, 31P-NMR) and solid state (13C, 15N and 31P-CPMAS NMR) were determined. Peer reviewed
Phosphonate degradation by Spirulina strains: cyanobacterial biofilters for the removal of anticorrosive polyphosphonates from wastewater
2011
The ability of Spirulina spp. to metabolize the recalcitrant xenobiotic Dequest 2054(®) [hexamethylenediamine-N,N,N',N'-tetrakis(methylphosphonic acid)], a CaSO(4) inhibitor used for boiler treatment and reverse osmosis desalination, was investigated. The compound served as sole source of phosphorus, but not of nitrogen, for cyanobacterial growth. In vivo utilization was followed by (31)P NMR analysis. The disappearance of the polyphosphonate proceeded only with actively dividing cells, and no release of inorganic phosphate was evident. However, no difference was found between P-starved and P-fed cultures. Maximal utilization reached 1.0 ± 0.2 mmoll(-1), corresponding to 0.56 ± 0.11 mmol g(…
Phosphonates as Unique Components of Plant Seeds—A Promising Approach to Use Phosphorus Profiles in Plant Chemotaxonomy
2021
Phosphorus is one of the most important elements essential for all living beings. Plants accumulate and store phosphorous in various forms that have diverse physiological and biochemical functions. In this study, we determine and then examine the phosphorus profiles of seeds of plants belonging to different taxa based on extractable inorganic phosphates and organic forms of phosphorus. We paid particular attention to the presence of natural phosphonates in the tested materials. The inorganic phosphates were determined colorimetrically, whereas phosphorus profiles were created by using 31P NMR spectroscopy. Our study on phosphorus profiles revealed that the obtainedsets of data vary signific…
Retrospective evaluation of persistence in osteoporosis therapy with oral bisphosphonates in Italy: the TOBI study
2019
The patients’ persistence with osteoporosis treatments is low. This retrospective, multicenter survey showed that almost 30% of osteoporotic patients discontinued the treatment within the first 6 months and that those taking drinkable bisphosphonates were less likely to interrupt the therapy; instead, the use of generic bisphosphonates was associated to a more precocious interruption. Purpose: Low persistence with osteoporosis medications is associated with higher fracture risk. This study aimed to assess the persistence to treatment with oral bisphosphonates among Italian osteoporotic patients under treatment for at least 6 months and to evaluate whether the different oral formulations of …
Oxidative stress in bisphosphonate-related osteonecrosis of the jaws
2013
Objectives To analyze whether oxidative stress (OS) changes are present in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) versus controls. Materials and Methods Oxidative stress was analyzed in serum and unstimulated saliva of three groups: Group 1 consisted of 24 patients who had been treated with intravenous bisphosphonates (ivBPs) and developed BRONJ, group 2 consisted of 20 patients who had received ivBPs and did not develop BRONJ, and group 3 comprised 17 control subjects. Reduced glutathione (GSH), malondialdehyde (MDA), oxidized glutathione (GSSG), and 8–oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dG) levels, as well as the GSSG/GSH ratio, were measured. Results Me…
Development of a [177Lu]BPAMD Labeling Kit and an Automated Synthesis Module for Routine Bone Targeted Endoradiotherapy
2015
Painful bone lesions, both benign and metastatic, are often managed using conventional analgesics. However, the treatment response is not immediate and is often associated with side-effects. Radionuclide therapy is used for pain palliation in bone metastases as well as some benign neoplasms. Endoradiotherapy has direct impact on the pain-producing bone elements, and hence, response is significant, with minimal or no side-effects. A new potential compound for endoradiotherapy is [(177)Lu]BPAMD. It combines a highly affine bisphosphonate, covalently bridged with DOTA through an amide bond, with the low-energy β(-) emitting therapeutic radiolanthanide (177)Lu. For routine chemical application,…
Serum interleukin-6 in patients with metastatic bone disease: correlation with cystatin C.
2008
The clinical significance of serum interleukin-6 (IL-6) and its correlation with cystatin C (Cyst C), an endogenous inhibitor of cysteine proteinase cathepsin K, was investigated by immunoassays in patients with bone metastasis from breast cancer (BCa) or prostate cancer (PCa). Additional studies were also performed in these patients to assess the effects of zoledronic acid (ZA) administration on the circulating levels of these molecules. Mean IL-6 and Cyst C serum concentrations were signifi- cantly increased in BCa patients and in patients with primary osteoporosis (PU) compared to healthy subjects (HS). However, Cyst C, but not IL-6, resulted significantly more elevated in BCa patients t…
A DOTA based bisphosphonate with an albumin binding moiety for delayed body clearance for bone targeting
2016
Radiolabeled bisphosphonates are commonly used in the diagnosis and therapy of bone metastases. Blood clearance of bisphosphonates is usually fast and only 30%-50% of the injected activity is retained in the skeleton, while most of the activity is excreted by the urinary tract. A longer blood circulation may enhance accumulation of bisphosphonate compounds in bone metastases. Therefore, a chemically modified macrocyclic bisphosphonate derivative with an additional human albumin binding entity was synthesized and pharmacokinetics of its complex was evaluated. The DOTA-bisphosphonate conjugate BPAMD was compared against the novel DOTAGA-derived albumin-binding bisphosphonate DOTAGA(428-d-Lys)…
68Ga-BPAMD: PET-imaging of bone metastases with a generator based positron emitter
2012
Abstract Purpose Bone metastases are a serious aggravation for patients suffering from cancer. Therefore, early recognition of bone metastases is of great interest for further treatment of patients. Bisphosphonates are widely used for scintigraphy of bone lesions with 99m Tc. Using the 68 Ge/ 68 Ga generator together with a macroyclic bisphosphonate a comparable PET-tracer comes into focus. Procedures The bisphosphonate DOTA-conjugated ligand BPAMD was labelled with 68 Ga. [ 68 Ga]BPAMD was evaluated in vitro concerning binding to hydroxyapatite and stability. The tracer's in vivo accumulation was determined on healthy rats and bone metastases bearing animals by μ-PET. Results BPAMD was lab…