Transport of Therapeutic Vanadium and Ruthenium Complexes by Blood Plasma Components

J.      Costa Pessoa; I.      Tomaz

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