The synthesis and structural characterization of a newly synthesized mononuclear rhodium(III) complex, Rhtrz, with a ligand (2,2,6-bis((4S,7R)-7,8,8-trimethyl-4,5,6,7-tetrahydro-1H-4,7-methanoindazol-3-yl)pyridine) and a ligand of 1,2,4-triazole, are presented in this paper. The kinetic interactions of the Rhtrz complex with essential biomolecules such as 5-GMP, L-Met, and GSH were examined. The study of the biological interactions was focused on the binding properties of the Rhtrz complex with CT-DNA and serum albumin. These interactions were investigated using UV-vis spectrophotometry, fluorescence spectroscopy, viscosity measurements, thermal denaturation studies, and electrophoresis. Fluorescence competition experiments with site-markers for BSA were used to locate the binding site of the Rhtrz-complex to the BSA. Molecular docking studies were carried out to obtain detailed binding information of the complex with CT-DNA, BSA, and HSA. Furthermore, the apparent distance between the donor (HSA) and acceptor (Rhtrz) was determined using fluorescence resonance energy transfer (FRET). The thermodynamic properties and relative stabilities of the Rhtrz complex were examined, constructing the two model equation by DFT calculations (B3LYP(CPCM)/LANL2DZp). In vitro cytotoxicity and redox status on the human epithelial colorectal cancer cell line (HCT-116) and healthy human fibroblast cell line (MRC-5) were also investigated.

The numerous side effects of platinum based chemotherapy has led to the design of new therapeutics with platinum replaced by another transition metal. Here, we investigated the interactions of previously reported copper(II) complexes containing S-isoalkyl derivatives, the salicylic acid with guanosine-5′-monophosphate and calf thymus DNA (CT-DNA) and their antitumor effects, in a colon carcinoma model. All three copper(II) complexes exhibited an affinity for binding to CT-DNA, but there was no indication of intercalation or the displacement of ethidium bromide. Molecular docking studies revealed a significant affinity of the complexes for binding to the minor groove of B-form DNA, which coincided with DNA elongation, and a higher affinity for binding to Z-form DNA, supporting the hypothesis that the complex binding to CT-DNA induces a local transition from B-form to Z-form DNA. These complexes show a moderate, but selective cytotoxic effect toward colon cancer cells in vitro. Binuclear complex of copper(II) with S-isoamyl derivative of thiosalicylic acid showed the highest cytotoxic effect, arrested tumor cells in the G2/M phase of the cell cycle, and significantly reduced the expression of inflammatory molecules pro-IL-1β, TNF-α, ICAM-1, and VCAM-1 in the tissue of primary heterotopic murine colon cancer, which was accompanied by a significantly reduced tumor growth and metastases in the lung and liver.

Three novel Zn(II) complexes [ZnCl₂(H₂L^tBu)], [ZnCl₂(Me₂L^tBu)] and [Zn₂Cl₄(H₂L^CatBiPyPh)₂] (where H₂L^tBu is 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine, Me₂L^tBu is 2,6-bis(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)pyridine and H₂L^CatBiPyrPh is 1,2-bis((5-phenyl-1H-pyrazol-3-yl)methoxy)benzene) were synthesized and characterized using various spectroscopic techniques, including UV-vis, IR, ¹D (¹H and ¹³C) and 2D (¹H–¹H COSY) NMR. The structures of complexes [ZnCl₂(H₂L^tBu)] and [Zn₂Cl₄(H₂L^CatBiPyPh)₂] were elucidated through X-ray crystallography. The interactions of the complexes with CT-DNA and human serum albumin (HSA) were investigated using UV-vis spectroscopy and fluorescence emission titration. All examined complexes exhibited quenching constant, K_sv, values in the order of 10⁴ with CT-DNA. Constant values followed the trend [ZnCl₂(Me₂L^tBu)] < [Zn₂Cl₄(H₂L^CatBiPyPh)₂] < [ZnCl₂(H₂L^tBu)]. The results indicated a moderate interaction between the complexes and HSA. In terms of cytotoxic activity, the zinc(II) complexes significantly decreased the viability of colon (HCT-116) and pancreatic (MIA PaCa-2) cancer cell lines, where the effect on pancreatic cells after 72 h is especially emphasized. The most pronounced occurrence of apoptosis, as the dominant type of complex-induced cell death, was associated with complex [ZnCl₂(H₂L^tBu)], while necrosis was observed at lower percentages in all investigated treatments. All complexes demonstrated downregulation of the tumor suppressor gene TP53 (homo sapiens tumor protein p53). Treatment with [ZnCl₂(H₂L^tBu)] resulted in downregulation of TP53, CASP3 (Caspase 3) and IGF1R (insulin-like growth factor 1), potentially impairing the effective apoptotic process and reducing cell proliferation.