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

Hasić R, Serezlić MK, Caković A, Bogojeski J, Nikodijević D, Milutinović M, Stanojević A, Čavić M, Egorov AV, Komolkin AV, Kornyakov IV, Scheurer A, Puchta R, Soldatović TV (2025)

Publication Type: Journal article

Publication year: 2025

Journal

New Journal of Chemistry Royal Society of Chemistry

DOI: 10.1039/d5nj00043b

Abstract

Three novel Zn(ii) complexes [ZnCl2(H2LtBu)], [ZnCl2(Me2LtBu)] and [Zn2Cl4(H2LCatBiPyPh)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(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.

Authors with CRIS profile

Andreas Scheurer Lehrstuhl für Anorganische und Allgemeine Chemie Ralph Puchta Lehrstuhl für Anorganische und Metallorganische Chemie

Involved external institutions

State University of Novi Pazar

Serbia (RS) University of Kragujevac

Serbia (RS) Institute of Oncology and Radiology of Serbia / Institut za onkologiju i radiologiju Srbije

Serbia (RS) Saint Petersburg State University (SPbU) / Санкт-Петербургский государственный университет (СПбГУ)

Russian Federation (RU)

How to cite

APA:

Hasić, R., Serezlić, M.K., Caković, A., Bogojeski, J., Nikodijević, D., Milutinović, M.,... Soldatović, T.V. (2025). New bis-pyrazolate zinc(ii) complexes as potential anticancer drugs: from structure to anticancer activity. New Journal of Chemistry. https://doi.org/10.1039/d5nj00043b

MLA:

Hasić, Rušid, et al. "New bis-pyrazolate zinc(ii) complexes as potential anticancer drugs: from structure to anticancer activity." New Journal of Chemistry (2025).

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