Polydentate nitrogen-containing donor ligands derived from poly(pyrazol-1-yl)methanes bearing organic functional groups on the bridging carbon have recently attracted considerable attention and their coordination chemistry towards main group and transition metals have been extensively studied [1]. Recently we designed and synthetized two carboxylated heteroscorpionate ligands (LH, [HC(CO2H)(pz)2] and LMe, [HC(CO2H)(pzMe2)2]), and the related 5-nitroimidazole conjugated heteroscorpionate ligands named LHMN and LMeMN [2] (Fig. 1) by direct coupling of preformed side chain acid with 5-nitroimidazole. In particular the copper(II) complexes (LRMN)2CuCl2 and the water soluble copper(I) complexes [(LRMN)Cu(PTA)2](PF6) (R = H or Me) have been prepared and evaluated for their cytotoxic activity towards a panel of several human tumour cell lines [3]. The ligands LH and LMe have also been functionalized with the potent NMDA receptor antagonist (6,6-diphenyl-1,4-dioxan-2-yl)methanamine, which showed a significant cytotoxic activity on MCF7 human breast cancer cell lines, highly expressing NMDA receptors [4], affording the conjugated derivatives LHNMDA and LMeNMDA (Fig. 1) used for the preparation of stable Cu(I/II) complexes. All the compounds were evaluated against a panel of human tumor cell lines derived from solid tumors. The research results suggest that these Cu(I/II) complexes might act through synergistic mechanisms of action due to the presence of the NMDA ligands and copper in the same chemical entity.

Rational design and biological evaluation of novel conjugated heteroscorpionate ligands and related Copper(I/II) complexes

Carlo Santini;Maura Pellei;BAGNARELLI, Luca;Cristina Cimarelli;Fabio Del Bello;Wilma Quaglia;Maria Beatrice Morelli;Consuelo Amantini;
2018-01-01

Abstract

Polydentate nitrogen-containing donor ligands derived from poly(pyrazol-1-yl)methanes bearing organic functional groups on the bridging carbon have recently attracted considerable attention and their coordination chemistry towards main group and transition metals have been extensively studied [1]. Recently we designed and synthetized two carboxylated heteroscorpionate ligands (LH, [HC(CO2H)(pz)2] and LMe, [HC(CO2H)(pzMe2)2]), and the related 5-nitroimidazole conjugated heteroscorpionate ligands named LHMN and LMeMN [2] (Fig. 1) by direct coupling of preformed side chain acid with 5-nitroimidazole. In particular the copper(II) complexes (LRMN)2CuCl2 and the water soluble copper(I) complexes [(LRMN)Cu(PTA)2](PF6) (R = H or Me) have been prepared and evaluated for their cytotoxic activity towards a panel of several human tumour cell lines [3]. The ligands LH and LMe have also been functionalized with the potent NMDA receptor antagonist (6,6-diphenyl-1,4-dioxan-2-yl)methanamine, which showed a significant cytotoxic activity on MCF7 human breast cancer cell lines, highly expressing NMDA receptors [4], affording the conjugated derivatives LHNMDA and LMeNMDA (Fig. 1) used for the preparation of stable Cu(I/II) complexes. All the compounds were evaluated against a panel of human tumor cell lines derived from solid tumors. The research results suggest that these Cu(I/II) complexes might act through synergistic mechanisms of action due to the presence of the NMDA ligands and copper in the same chemical entity.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/406406
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