Investigating the antiproliferative activities of new Cu-II complexes with pyridine hydrazone derivatives of nalidixic acid

Author(s):Show less -

Bergamini, Fernando R. G. ; Nunes, Julia H. B. ; Manzano, Carlos Marrote ; de Carvalho, Marcos Alberto ; Ribeiro, Marcos Antonio ; Ruiz, Ana Lucia Tasca Gois ; de Carvalho, Joao Ernesto ; Lustri, Wilton Rogerio ; de Paiva, Raphael Enoque Ferraz ; Portes, Marcelo Cecconi ; Ferreira, Ana Maria da Costa ; Corbi, Pedro Paulo

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 234, p. 11-pg., 2022-09-01.

Abstract

To further explore the structural features and potential antibacterial and antitumor activities of polynuclear CuII coordination compounds with nalidixic acid (nx) derivatives, new complexes bearing nx hydrazones with Npyridinyl moieties substituted at positions 2 and 3 (h2py and h3py) were synthesized. Complexes [Cu3 (C18H16N5O2)2(C18H17N5O2)2(H2O)](4)BF4.H2O (1), and [Cu-3(C18H16N5O2)(2)(C18H17N5O2)(2)(H2O)(3)](4)BF4.3H(2)O (%) (2) were synthesized using h2py and h3py with Cu(BF4)(2).nH(2)O as precursor, whereas the [Cu(C18H17N5O2) Cl2].0.5H(2)O complex (3) was synthesized with h2py and CuCl2 & BULL;2H2O. Crystallographic studies of complex 1, showed that coordination of hydrazones to CuII occurs by tridentate modes of type kappa 3(O,N,N') as well as bidentate modes of type kappa 2(O',N "). Complexes 1, 2 and 3 had their antiproliferative activities evaluated in vitro against a panel of tumor cells by the determination of GI50 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 pi-stacking interactions with DNA. The TN species were also shown to be possible minor groove binders. (AU)

• FAPESP's process: 21/08717-8 - Synthesis of copper, silver and gold complexes involving nucleotide analogues in the search of new alternatives for the treatment of ovarian cancer
• Grantee: Pedro Paulo Corbi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 18/12590-0 - Synthesis of metal complexes with bioactive N,N or N,O-coordinating ligands for use in sustainable delivery system based on bacterial cellulose
• Grantee: Wilton Rogério Lustri
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/25995-6 - New Ag(I), Pd(II) and Pt(II) metal complexes with ligands used for the treatment of Tuberculosis: synthesis and in vitro evaluation of antimicrobial and antiproliferative activities
• Grantee: Carlos Marrote Manzano
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/25114-4 - Synthesis of New Ag(I), Cu(II), Pd(II) and Pt(II) complexes based on sulfonamides and derivatives: antibacterial activities and application prospects on skin critically colonized wounds.
• Grantee: Pedro Paulo Corbi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/12062-4 - Synthesis, characterization and studies of interaction with biomolecules of metal complexes containing biologically active ligands: a strategy in the preparation of new agents with antibacterial and antiviral activities
• Grantee: Pedro Paulo Corbi
• Support Opportunities: Regular Research Grants