A comparative study of adduct formation between the anticancer ruthenium(III) compound HInd trans-[RuCl4(Ind)2] and serum proteins.
Formation of adducts between the antitumor ruthenium(III) complex [HInd]trans-[RuCl(4)(Ind)(2)] (KP1019) and the plasma proteins serum albumin and serum transferrin was investigated by UV-vis spectroscopy, for metal-to-protein ratios ranging from 1:1 to 5:1. In both cases, formation of tight metal-protein conjugates was observed. Similar spectroscopic features were observed for both albumin and transferrin derivatives implying a similar binding mode of the ruthenium species to these proteins. Surface histidines are the probable anchoring sites for the bound ruthenium(III) ions in line with previous crystallographic results. In order to assess the stability of the KP1019-protein adducts the influence of pH, reducing agents and chelators was analysed by UV-vis spectroscopy. Notably, there was no effect of addition of EDTA on the UV-vis spectra of the conjugates. The pH-stability was high in the pH range 5-8. Experiments with sodium ascorbate showed that there was just some alteration of selected bands. The implications of the present results are discussed in relation to the pharmacological behavior of this novel class of antitumor compounds.
Piccioli
F
F
Department of Chemistry, University of Florence, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Florence, Italy.
Sabatini
S
S
Messori
L
L
Orioli
P
P
Hartinger
Ch G
ChG
Keppler
B K
BK
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017975:Ruthenium Compounds; D012710:Serum Albumin, Bovine / Q000737:chemistry* / Q000378:metabolism; D014168:Transferrin / Q000737:chemistry*
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; D014168:Transferrin; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); C436300:tetrachlorobis(indazole)ruthenate(III); D012710:Serum Albumin, Bovine; D004121:Dimethyl Sulfoxide