The thionated derivative of the antibacterial agent nalidixic acid and its organoruthenium complex were prepared and their crystal structures were determined. The aqueous stability of the complex was studied and, unlike the nalidixicato complex, increased stability of the ruthenium complex in aqueous solution was observed with only a minor degree of thionalidixicato ligand dissociated within a week. While the derivatization caused the antibacterial activity of the ligand against E. coli to decrease, the cytotoxicity of the complex against three cancer cell lines was significantly increased and the inhibitory potency against two enzymes of the cathepsin family was increased by 10-fold.
COBISS.SI-ID: 36100357
Continuing the study of the physico-chemical and biological properties of ruthenium-quinolone adducts, four novel complexes with the general formula [Ru([9]aneS3)(dmso-κS)(quinolonato-κ2O,O)](PF6), containing the quinolones levofloxacin (1), nalidixic acid (2), oxolinic acid (3), and cinoxacin (4), were prepared and characterized in solid state as well as in solution. Contrary to their organoruthenium analogues, these complexes are generally relatively stable in aqueous solution as substitution of the dmso ligand is slow and not quantitative, and a minor release of the quinolonato ligand is observed only in the case of 4. The complexes bind to serum proteins displaying relatively high binding constants. DNA binding was studied using UV-Vis spectroscopy, cyclic voltammetry and performing viscosity measurements of CT DNA solutions in the presence of complexes 1–4. These experiments show that the ruthenium complexes interact with DNA via intercalation. Compounds 2 and 4 exhibit a weak inhibition of cathepsins B and S, which are involved in the progression of a number of diseases, including cancer. Furthermore, complexes displayed moderate cytotoxicity when tested on the HeLa cell line.
COBISS.SI-ID: 1610287
Conjoint liquid chromatography (CLC) on monolithic convective interaction media (CIM) disks coupled on-line to UV and inductively coupled plasma mass spectrometry (ICP-MS) detectors was used in speciation analysis of Pt in human serum spiked with Pt-based chemotherapeutics. CIM Protein G and CIM DEAE disks were assembled together in a single housing forming a CLC monolithic column. Such a set-up allows rapid two-dimensional separation by affinity and ion-exchange (IE) modes to be carried out in a single chromatographic run. Separated Pt species were quantified by post-column isotope dilution—ICP-MS. The method developed may be reliably applied in preclinical and clinical studies of the kinetics of the interaction and distribution of different metallodrugs with proteins in blood serum.
COBISS.SI-ID: 26734631
The scientific article presents the results obtained in the framework of the study with two main objectives: to determine influence of electroporation on the cytotoxic and antitumor effect of a ruthenium(III) compound with hampered transmembrane transport, (imH)[trans-RuCl4(im)2] (KP418) in vitro and in vivo and to determine changes in metastatic potential of cells after ECT with KP418 in vitro. In addition, platinum(II) compound cisplatin and ruthenium(III) compound NAMI-A were included in the experiments as reference compounds. A study showed that electroporation leads to increased cellular accumulation of ruthenium and increased cytotoxicity of KP418 in murine melanoma cell lines B16-F1 and B16-F10. In addition, the results showed that the metastatic potential of cells which survived ECT with KP418 or NAMI-A does not change in vitro: resistance to detachment, invasiveness and re-adhesion of cells after ECT is not affected. Experiments in murine tumor models in vivo showed that ECT with KP418 does not have any antitumor effect.
COBISS.SI-ID: 1722671
An important step in pharmacological characterisation of a candidate drug is the study of the drugs interactions with serum proteins. In the present work, conjoint liquid chromatography (CLC) was used for separation of ruthenium (Ru)-based drug candidates in human serum. CIM Protein G and CIM DEAE disks were assembled together in a single housing forming a CLC monolithic column. During isocratic elution immunoglobulins (IgG) were retained by the Protein G disk enabling subsequent separation of unbound Ru species from Ru species bound to human serum transferrin (Tf) and albumin (HSA) on the CIM DEAE disk. Protein elution was followed on-line with UV detection at 278 nm, while the separated Ru species were monitored and quantified by post-column isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS). The instrumental set-up enabled fast two-dimensional separation by affinity and ion-exchange modes to be carried out in a single chromatographic run. Two Ru-based chemotherapeutics: a newly synthesised compound chlorido(η6-p-cymene)(nalidixicato-κ2O,O)Ru(II) and (H2im)[trans-Ru(III)Cl4(Him)2] (KP418), which is currently undergoing preclinical studies studies, were investigated.
COBISS.SI-ID: 28056103