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

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Autori principali: Hasić, Rušid, Kolenović Serezlić, Majda, Cakovic, Angelina, Bogojeski, Jovana, Nikodijević,, Danijela, Ćurčić Milutinović, Milena, Stanojević, Aleksandra, Čavić, Milena, Egorov, Andrei V., Komolkin, Andrei, Kornyakov, Ilya V., Scheurer, Andreas, Puchta, Ralph, Soldatovic, Tanja V.
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Lingua:inglese
Pubblicazione: Zenodo 2025
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author Hasić, Rušid
Kolenović Serezlić, Majda
Cakovic, Angelina
Bogojeski, Jovana
Nikodijević,, Danijela
Ćurčić Milutinović, Milena
Stanojević, Aleksandra
Čavić, Milena
Egorov, Andrei V.
Komolkin, Andrei
Kornyakov, Ilya V.
Scheurer, Andreas
Puchta, Ralph
Soldatovic, Tanja V.
author_facet Hasić, Rušid
Kolenović Serezlić, Majda
Cakovic, Angelina
Bogojeski, Jovana
Nikodijević,, Danijela
Ćurčić Milutinović, Milena
Stanojević, Aleksandra
Čavić, Milena
Egorov, Andrei V.
Komolkin, Andrei
Kornyakov, Ilya V.
Scheurer, Andreas
Puchta, Ralph
Soldatovic, Tanja V.
contents <h3>Abstract</h3> <div> <div> <p>Three novel Zn(II) complexes <strong>[ZnCl<sub>2</sub>(H<sub>2</sub>L<sup><em>t</em>Bu</sup>)]</strong>, <strong>[ZnCl<sub>2</sub>(Me<sub>2</sub>L<sup><em>t</em>Bu</sup>)]</strong> and <strong>[Zn<sub>2</sub>Cl<sub>4</sub>(H<sub>2</sub>L<sup>CatBiPyPh</sup>)<sub>2</sub>]</strong> (where H<sub>2</sub>L<sup><em>t</em>Bu</sup> is 2,6-bis(5-<em>tert</em>-butyl-1<em>H</em>-pyrazol-3-yl)pyridine, Me<sub>2</sub>L<sup><em>t</em>Bu</sup> is 2,6-bis(5-<em>tert</em>-butyl-1-methyl-1<em>H</em>-pyrazol-3-yl)pyridine and H<sub>2</sub>L<sup>CatBiPyrPh</sup> is 1,2-bis((5-phenyl-1<em>H</em>-pyrazol-3-yl)methoxy)benzene) were synthesized and characterized using various spectroscopic techniques, including UV-vis, IR, <sup>1</sup>D (<sup>1</sup>H and <sup>13</sup>C) and 2D (<sup>1</sup>H–<sup>1</sup>H COSY) NMR. The structures of complexes <strong>[ZnCl<sub>2</sub>(H<sub>2</sub>L<sup><em>t</em>Bu</sup>)]</strong> and <strong>[Zn<sub>2</sub>Cl<sub>4</sub>(H<sub>2</sub>L<sup>CatBiPyPh</sup>)<sub>2</sub>]</strong> 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, <em>K</em><sub>sv</sub>, values in the order of 10<sup>4</sup> with CT-DNA. Constant values followed the trend <strong>[ZnCl<sub>2</sub>(Me<sub>2</sub>L<sup><em>t</em>Bu</sup>)]</strong> < <strong>[Zn<sub>2</sub>Cl<sub>4</sub>(H<sub>2</sub>L<sup>CatBiPyPh</sup>)<sub>2</sub>]</strong> < <strong>[ZnCl<sub>2</sub>(H<sub>2</sub>L<sup><em>t</em>Bu</sup>)]</strong>. 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 <strong>[ZnCl<sub>2</sub>(H<sub>2</sub>L<sup><em>t</em>Bu</sup>)]</strong>, while necrosis was observed at lower percentages in all investigated treatments. All complexes demonstrated downregulation of the tumor suppressor gene <em>TP53</em> (<em>homo sapiens</em> tumor protein p53). Treatment with <strong>[ZnCl<sub>2</sub>(H<sub>2</sub>L<sup><em>t</em>Bu</sup>)]</strong> resulted in downregulation of <em>TP53</em>, <em>CASP3</em> (<em>Caspase 3</em>) and <em>IGF1R</em> (insulin-like growth factor 1), potentially impairing the effective apoptotic process and reducing cell proliferation.</p> </div> </div>
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publishDate 2025
publisher Zenodo
record_format zenodo
spellingShingle New bis-pyrazolate zinc(ii) complexes as potential anticancer drugs: from structure to anticancer activity
Hasić, Rušid
Kolenović Serezlić, Majda
Cakovic, Angelina
Bogojeski, Jovana
Nikodijević,, Danijela
Ćurčić Milutinović, Milena
Stanojević, Aleksandra
Čavić, Milena
Egorov, Andrei V.
Komolkin, Andrei
Kornyakov, Ilya V.
Scheurer, Andreas
Puchta, Ralph
Soldatovic, Tanja V.
anticancer activity
anticancer drugs
spectroscopic techniques
<h3>Abstract</h3> <div> <div> <p>Three novel Zn(II) complexes <strong>[ZnCl<sub>2</sub>(H<sub>2</sub>L<sup><em>t</em>Bu</sup>)]</strong>, <strong>[ZnCl<sub>2</sub>(Me<sub>2</sub>L<sup><em>t</em>Bu</sup>)]</strong> and <strong>[Zn<sub>2</sub>Cl<sub>4</sub>(H<sub>2</sub>L<sup>CatBiPyPh</sup>)<sub>2</sub>]</strong> (where H<sub>2</sub>L<sup><em>t</em>Bu</sup> is 2,6-bis(5-<em>tert</em>-butyl-1<em>H</em>-pyrazol-3-yl)pyridine, Me<sub>2</sub>L<sup><em>t</em>Bu</sup> is 2,6-bis(5-<em>tert</em>-butyl-1-methyl-1<em>H</em>-pyrazol-3-yl)pyridine and H<sub>2</sub>L<sup>CatBiPyrPh</sup> is 1,2-bis((5-phenyl-1<em>H</em>-pyrazol-3-yl)methoxy)benzene) were synthesized and characterized using various spectroscopic techniques, including UV-vis, IR, <sup>1</sup>D (<sup>1</sup>H and <sup>13</sup>C) and 2D (<sup>1</sup>H–<sup>1</sup>H COSY) NMR. The structures of complexes <strong>[ZnCl<sub>2</sub>(H<sub>2</sub>L<sup><em>t</em>Bu</sup>)]</strong> and <strong>[Zn<sub>2</sub>Cl<sub>4</sub>(H<sub>2</sub>L<sup>CatBiPyPh</sup>)<sub>2</sub>]</strong> 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, <em>K</em><sub>sv</sub>, values in the order of 10<sup>4</sup> with CT-DNA. Constant values followed the trend <strong>[ZnCl<sub>2</sub>(Me<sub>2</sub>L<sup><em>t</em>Bu</sup>)]</strong> < <strong>[Zn<sub>2</sub>Cl<sub>4</sub>(H<sub>2</sub>L<sup>CatBiPyPh</sup>)<sub>2</sub>]</strong> < <strong>[ZnCl<sub>2</sub>(H<sub>2</sub>L<sup><em>t</em>Bu</sup>)]</strong>. 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 <strong>[ZnCl<sub>2</sub>(H<sub>2</sub>L<sup><em>t</em>Bu</sup>)]</strong>, while necrosis was observed at lower percentages in all investigated treatments. All complexes demonstrated downregulation of the tumor suppressor gene <em>TP53</em> (<em>homo sapiens</em> tumor protein p53). Treatment with <strong>[ZnCl<sub>2</sub>(H<sub>2</sub>L<sup><em>t</em>Bu</sup>)]</strong> resulted in downregulation of <em>TP53</em>, <em>CASP3</em> (<em>Caspase 3</em>) and <em>IGF1R</em> (insulin-like growth factor 1), potentially impairing the effective apoptotic process and reducing cell proliferation.</p> </div> </div>
title New bis-pyrazolate zinc(ii) complexes as potential anticancer drugs: from structure to anticancer activity
topic anticancer activity
anticancer drugs
spectroscopic techniques
url https://doi.org/10.1039/D5NJ00043B