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Investigating the antiproliferative activities of new Cu complexes with pyridine hydrazone derivatives of nalidixic acid. | LitMetric

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Article Abstract

To further explore the structural features and potential antibacterial and antitumor activities of polynuclear Cu coordination compounds with nalidixic acid (nx) derivatives, new complexes bearing nx hydrazones with N-pyridinyl moieties substituted at positions 2 and 3 (h2py and h3py) were synthesized. Complexes [Cu(CHNO)(CHNO)(HO)]4BF∙HO (1), and [Cu(CHNO)(CHNO)(HO)]4BF∙3HO (%) (2) were synthesized using h2py and h3py with Cu(BF)∙nHO as precursor, whereas the [Cu(CHNO)Cl]∙0.5HO complex (3) was synthesized with h2py and CuCl∙2HO. Crystallographic studies of complex 1, showed that coordination of hydrazones to Cu occurs by tridentate modes of type κ(O,N,N') as well as bidentate modes of type κ(O',N″). Complexes 1, 2 and 3 had their antiproliferative activities evaluated in vitro against a panel of tumor cells by the determination of GI values. Complexes 1 and 2 were more active than complex 3, suggesting an effect of the complex charge on their activities. The interactions of such complexes towards bovine serum albumin (BSA) and DNA plasmid (pGEX-4 T1) were investigated using fluorescence spectroscopy and gel electrophoresis. All complexes were shown to interact with the DNA model as metallonucleases, but no interaction with BSA was observed. DNA molecular docking of complex 1 encompassing both its trinuclear (TN) form and a possible mononuclear (MN) derivative suggests that naphthyridyl ring performs π-stacking interactions with DNA. The TN species were also shown to be possible minor groove binders.

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http://dx.doi.org/10.1016/j.jinorgbio.2022.111881DOI Listing

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