20.500.12556/RUL-133378 Binding kinetics of ruthenium pyrithione chemotherapeutic candidates to human serum proteins studied by HPLC-ICP-MS The development of ruthenium-based complexes for cancer treatment requires a variety of pharmacological studies, one of them being a drug’s binding kinetics to serum proteins. In this work, speciation analysis was used to study kinetics of ruthenium-based drug candidates with human serum proteins. Two ruthenium (Ru) complexes, namely [(η$^6$-p-cymene)Ru(1-hydroxypyridine-2(1H)-thionato)Cl] (1) and [(η$^6$-p-cymene)Ru(1-hydroxypyridine-2(1H)-thionato)pta]PF$_6$ (2) (where pta = 1,3,5-triaza-7- phosphaadamantane), were selected. Before a kinetics study, their stability in relevant media was confirmed by nuclear magnetic resonance (NMR). Conjoint liquid chromatography (CLC) monolithic column, assembling convective interaction media (CIM) protein G and diethylamino (DEAE) disks, was used for separation of unbound Ru species from those bound to human serum transferrin (Tf), albumin (HSA) and immunoglobulins G (IgG). Eluted proteins were monitored by UV spectrometry (278 nm), while Ru species were quantified by post-column isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS). Binding kinetics of chlorido (1) and pta complex (2) to serum proteins was followed from 5 min up to 48 h after incubation with human serum. Both Ru complexes interacted mainly with HSA. Complex (1) exhibited faster and more extensive interaction with HSA than complex (2). The equilibrium concentration for complex (1) was obtained 6 h after incubation, when about 70% of compound was bound to HSA, 5% was associated with IgG, whereas 25% remained unbound. In contrast, the rate of interaction of complex (2) with HSA was much slower and less extensive and the equilibrium concentration was obtained 24 h after incubation, when about 50% of complex (2) was bound to HSA and 50% remained unbound. ruthenium-based chemotherapeutics drug candidates pyrithione kinetics study human serum speciation analysis CLC monolithic chromatography CIM Protein G DEAE disks UV spectrometry isotope dilution inductively coupled plasma mass spectrometry true false true Angleški jezik Ni določen Članek v reviji 2021-11-24 15:09:45 2021-11-24 15:09:46 2022-09-12 04:16:04 0000-00-00 00:00:00 2020 0 0 14 str. iss. 7, art. 1512 Vol. 25 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 54 1420-3049 10.3390/molecules25071512 33282855 RAZ_Markovic_Katarina_2020.pdf RAZ_Markovic_Katarina_2020.pdf 1 FBFE167A75E892FC2CC7DFD70DBD3A76 fb791680c6f202facb82cae767c5eec23cdb9899b7aa0448c8ca3080bd49be9c 43f6f25e-4d30-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=151400 https://www.mdpi.com/1420-3049/25/7/1512 0 39a16d40-4d30-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=151399 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0