J1-4131 — Annual report 2012
1.
Factors that influence the antiproliferative activity of half sandwich Ru[sup]II-[9]aneS3 coordination compounds

We investigated the ability of half sandwich Ru(II) coordination compounds to act as DNA binders. The model reactions of three Ru(II)–[9]aneS3 complexes, i.e. Ru([9]aneS3)(en)Cl](PF6) (1), [Ru([9]aneS3)(bpy)Cl](PF6) (2), and [Ru([9]aneS3)(pic)Cl] (3) (where [9]aneS3 = 1,4,7-trithiacyclononane, en = 1,2-diaminoethane, pic = picolinate), with the guanine derivatives 9-methylguanine (9MeG), guanosine (Guo), and 5'-guanosine monophosphate (5'-GMP) were studied by NMR spectroscopy. All reactions lead to the formation of monofunctional adducts with the guanine derivatives N7-bonded to the Ru center. Two products, the complexes [Ru([9]aneS3)(en)(9MeG-N7)](PF6)2 (4) and [Ru([9]aneS3)(pic)(9MeG-N7)](PF6) (10), were structurally characterized also in the solid state by X-ray crystallography.

COBISS.SI-ID: 36106757
2.
Synthesis and biological evaluation of the thionated antibacterial agent nalidixic acid and its organoruthenium(II) complex

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
3.
The use of CIM-DEAE monolithic chromatography coupled to ICP-MS to study the distribution of cisplatin in human serum

CIM-DEAE-1 fast monolithic chromatography procedure was developed and applied for Pt speciation in serum of cancer patients receiving CDDP based chemotherapy. In these samples Pt was found to be bound in 87 to 93 % to HSA, in 2.6 to 6.4 % to Tf, and in 4.2 to 6.6 % as unbound CDDP species. To study cisplatin (CDDP) interactions with proteins, synthetic solutions of single standard proteins (albumin (HSA), transferrin (Tf) and γ-Globulins (IgG)) or their mixture, and human serum samples were spiked with CDDP and incubated at 37 °C for 24 h. Results of fractionation showed that more than 80 % of Pt in serum was eluted with proteins and remaining portion as low molecular mass species.

COBISS.SI-ID: 25587751