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Transport of Therapeutic Vanadium and Ruthenium Complexes by Blood Plasma Components

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Abstract:

Low molecular weight and high molecular weight metal ion binders present in blood plasma are shortly described. The binding of vanadium and ruthenium complexes by these components has received much attention, namely their interactions with human serum albumin and transferrin, and these studies are critically reviewed. The influence of the protein binding on the bioavailability of the prospective drugs, namely on the transport by blood plasma and uptake by cells is also discussed. It is concluded that vanadium compounds are mainly transported in blood by transferrin, but that no study has properly addressed the influence of albumin and transferrin in the vanadium uptake by cells. Ruthenium complexes bind strongly to HSA, most likely at the level of His residues, leading to the formation of stable adducts. If the kinetics of binding to this protein is fast enough, probably they are mainly transported by this serum protein. Nevertheless, at least for a few RuIII-complexes, hTf seems to play an active role in the uptake of ruthenium, while HSA may provide selectivity and higher activity for the compounds due to an enhanced permeability effect.





Keywords: 1-acid glycoprotein; BCM-EPR; Blood Plasma Components; Blood Serum Conditions; Bovine serum albumin (BSA); Chemotherapy; Circular dichroism; Cisplatin pharmaceuticals; D-binding protein; ESI-MS hyphenation; Erythrocytes; Gel electrophoresis techniques; HPLC-ICP-MS techniques; Human serum transferrin; Inductively Coupled Plasma - MS (ICP-MS); KP1019; NAMI; NAMI-A; NAMI-A type complexes; Osmium(II) analogue; RAPTA complexes; RAPTA-T; RuIII-complexes; Ruthenium; Ruthenium Complexes; Ruthenium complexes; Ruthenium-Protein Interactions; Synchrotron based techniques; Therapeutic Vanadium; VIVO-HSA-Carrier; VIVO-hTf-lactate; Vanadium; XANES spectroscopy; abscess tissues; albumin; albumin (HSA); amino-thiazole complexes; anion-exchange column; anti-arthritics; anti-bacterials; anti-hypertensive agent; anti-inflammatory agent; anti-parasitics; anti-trypanocidal agents; anti-virals; ascorbate; bismuth compounds; bismuth subsalicylate; blood stream complex; capillary zone electrophoresis (CZE); catecholamines; clotrimazole; cysteine; detect protein-bound; electron paramagnetic resonance (EPR); electrophoresis; emission spectroscopy (AES); enzymatic glycosylation; fetoprotein; fibrinogen; gastrointestinal disorders; globulins; gold complexes; heterometal-hTf complexes; human serum albumin; human serum transferrin; hydrolytic processes; immunoglobulin G; insulin-enhancers; insulin-enhancing activity; insulin-mimetics; ketoconazole; lactate; lactoferrin; low hydrosolubility; lymphatic drainage sys-tem; metal-containing drugs; metal-mediated antibiotics; metallodrugs; monoferric C-lobe; multi-task protein; organometallic complexes; ovotransferrin; oxalate; passive selective delivery; pharmacodynamics; pharmacokinetics; phosphate; picolinic acid; promote coagulation; prospective drugs; protein:complex ratios; radio-sensitizing agents; radiopharmaceuticals; ruthe-nium-HSA systems; ruthenium bioavailability; ruthenium complexes; ruthenium radioisotopes; semicarbazone derivative; serum protein binding; sodium nitroprusside; strongly binding drugs; therapeutic agents; therapeutic compound; transferrin receptor (TfR); transport in blood serum; tryptophan residue; vanadium bioavailability; vanadium speciation research

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986710793213742

Publication date: November 1, 2010

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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