TY - JOUR

T1 - New bis-pyrazolate zinc( ii ) complexes as potential anticancer drugs: from structure to anticancer activity

AU - Hasić, Rušid

AU - Serezlić, Majda Kolenović

AU - Caković, Angelina

AU - Bogojeski, Jovana

AU - Nikodijević, Danijela

AU - Milutinović, Milena

AU - Stanojević, Aleksandra

AU - Čavić, Milena

AU - Egorov, Andrei V.

AU - Komolkin, Andrei V.

AU - Kornyakov, Ilya V.

AU - Scheurer, Andreas

AU - Puchta, Ralph

AU - Soldatović, Tanja V.

PY - 2025/2/7

Y1 - 2025/2/7

N2 - Three novel Zn(ii) complexes [ZnCl2(H2LtBu)], [ZnCl2(Me2LtBu)] and [Zn2Cl4(H2LCatBiPyPh)2] (where H2LtBu is 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine, Me2LtBu is 2,6-bis(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)pyridine and H2LCatBiPyrPh 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(H2LtBu)] and [Zn2Cl4(H2LCatBiPyPh)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, Ksv, values in the order of 104 with CT-DNA. Constant values followed the trend [ZnCl2(Me2LtBu)] < [Zn2Cl4(H2LCatBiPyPh)2] < [ZnCl2(H2LtBu)]. 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(H2LtBu)], 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(H2LtBu)] 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.

AB - Three novel Zn(ii) complexes [ZnCl2(H2LtBu)], [ZnCl2(Me2LtBu)] and [Zn2Cl4(H2LCatBiPyPh)2] (where H2LtBu is 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine, Me2LtBu is 2,6-bis(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)pyridine and H2LCatBiPyrPh 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(H2LtBu)] and [Zn2Cl4(H2LCatBiPyPh)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, Ksv, values in the order of 104 with CT-DNA. Constant values followed the trend [ZnCl2(Me2LtBu)] < [Zn2Cl4(H2LCatBiPyPh)2] < [ZnCl2(H2LtBu)]. 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(H2LtBu)], 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(H2LtBu)] 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.

UR - https://www.mendeley.com/catalogue/febb1eda-2d93-36a2-94b4-bbbbc06958d0/

U2 - 10.1039/d5nj00043b

DO - 10.1039/d5nj00043b

M3 - Article

JO - New Journal of Chemistry

JF - New Journal of Chemistry

SN - 1144-0546

ER -