Transport of therapeutic vanadium and ruthenium complexes by blood plasma components.
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 Ru(III)-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.
Pessoa
J Costa
JC
Centro de Química Estrutural, Instituto Superior Técnico, TU Lisbon, Av. Rovisco Pais, 1049-001, Lisbon, Portugal. joao.pessoa@ist.utl.pt
Tomaz
I
I
D001692:Biological Transport; D001798:Blood Proteins / Q000378:metabolism*; D002986:Clinical Trials as Topic; D056831:Coordination Complexes / Q000097:blood* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008970:Molecular Weight; D011485:Protein Binding; D012428:Ruthenium / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D017975:Ruthenium Compounds / Q000097:blood* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D012429:Ruthenium Radioisotopes / Q000097:blood / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D012709:Serum Albumin / Q000378:metabolism; D013057:Spectrum Analysis; D014168:Transferrin / Q000378:metabolism; D014639:Vanadium / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D017968:Vanadium Compounds / Q000097:blood* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use
D001798:Blood Proteins; D056831:Coordination Complexes; D017975:Ruthenium Compounds; D012429:Ruthenium Radioisotopes; D012709:Serum Albumin; D014168:Transferrin; D017968:Vanadium Compounds; D014639:Vanadium; D012428:Ruthenium