In this study, we have developed a series of new monofunctional Ru(II) complexes of the general formula mer-[Ru(Cl-Ph-tpy)(N-N)Cl]Cl in which Cl-Ph-tpy is 4'-(4-chlorophenyl)-2,2':6',2″-terpyridine, N-N is a bidentate chelating ligand (1,2-diaminoethane (en, 1), 1,2-diaminocyclohexane (dach, 2) or 2,2'-bipyridine (bpy, 3)). All complexes were fully characterized by elemental analysis and spectroscopic techniques (IR, UV-Vis, 1D and 2D NMR). Their chemical behavior in aqueous solution was studied by UV-Vis and NMR spectroscopy showing that all compounds are relatively labile leading to the formation of the corresponding aqua species 1aq-3aq. Their DNA binding ability was evaluated by UV-Vis spectroscopy, fluorescence quenching measurements and viscosity measurements. Competitive studies with ethidium bromide (EB) showed that the complexes can displace DNA-bound EB, suggesting strong competition with EB (Ksv=1.1-2.7×104M-1). These experiments show that the ruthenium complexes interact with DNA via intercalation. The complexes bind to serum protein albumin displaying relatively high binding constants (Ksv=104-105M-1). Compound 3 displayed from high to moderate cytotoxicity against two cancer cell lines HeLa and A549 (with IC50ca. 12.7μM and 53.8μM, respectively), while complexes 1 and 2 showed only moderate cytotoxicity (with IC50ca. 84.8μM and 96.3μM, respectively) against HeLa cells. The cell cycle analysis (by flow cytometry) of HeLa and A549 cells treated with complex 3 shows minor changes on the cell cycle phase distribution.

New A-ring pyridine fused androstanes in 17a-homo-17-oxa (D-homo lactone), 17α-picolyl or 17(E)-picolinylidene series were synthesized and validated by X-ray crystallography, HRMS, IR and NMR spectroscopy. Novel compounds 3, 5, 8 and 12 were prepared by treatment of 4-en-3-one or 4-ene-3,6-dione D-modified androstane derivatives with propargylamine catalyzed by Cu(II), and evaluated for potential anticancer activity in vitro using human cancer cell lines and recombinant targets of steroidal anti-cancer drugs. Pyridine fusion to position 3,4 of the A-ring may dramatically enhance affinity of 17α-picolyl compounds for CYP17 while conferring selective antiproliferative activity against PC-3 cells. Similarly, pyridine fusion to the A-ring of steroidal D-homo lactones led to identification of new inhibitors of aldo–keto reductase 1C3, an enzyme targeted in acute myeloid leukemia, breast and prostate cancers. One A-pyridine D-lactone steroid 5 also has selective submicromolar antiproliferative activity against HT-29 colon cancer cells. None of the new derivatives have affinity for estrogen or androgen receptors in a yeast screen, suggesting negligible estrogenicity and androgenicity. Combined, our results suggest that A-ring pyridine fusions have potential in modulating the anticancer activity of steroidal compounds.

A novel Rh^III complex containing a pincer type nitrogen-donor ligand was synthesized; its interaction toward small biomolecules, duplex DNAs and RNA as well as CT-DNA and BSA was investigated.