Polynuclear copper(II) complexes with nalidixic acid hydrazones: Antiproliferative activity and selectivity assessment over a panel of tumor cells

Author(s):Show less -

Bergamini, Fernando R. G. ^{[1, 2]} ; Nunes, Julia H. B. ^[1] ; de Carvalho, Marcos A. ^[3] ; Ribeiro, Marcos A. ^[4] ; de Paiva, Paula P. ^[5] ; Banzato, Thais P. ^[6] ; Ruiz, Ana L. T. G. ^{[5, 6]} ; de Carvalho, Joao E. ^[5] ; Lustri, Wilton R. ^[7] ; Martins, Daniel O. T. A. ^[8] ; da Costa Ferreira, Ana M. ^[8] ; Corbi, Pedro P. ^[1]

Affiliation

^[1] Univ Campinas UNICAMP, Inst Chem, POB 6154, BR-13083970 Campinas, SP - Brazil

^[2] Fed Univ Uberlandia UFU, Inst Chem, BR-38400902 Uberlandia, MG - Brazil

^[3] Fed Univ Mato Grosso UFMT, Chem Dept, BR-78060900 Cuiaba, MT - Brazil

^[4] Fed Univ Espirito Santo UFES, Chem Dept, BR-29075910 Vitoria, ES - Brazil

^[5] Univ Campinas UNICAMP, Fac Pharmaceut Sci, BR-13083871 Campinas, SP - Brazil

^[6] Univ Campinas UNICAMP, Chem Biol & Agr Pluridisciplinary Res Ctr CPQBA, BR-13148218 Paulinia, SP - Brazil

^[7] Univ Araraquara UNIARA, Biol & Hlth Sci Dept, BR-14801320 Araraquara, SP - Brazil

^[8] Univ Sao Paulo, Inst Chem, Dept Fundamental Chem, BR-05508000 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Inorganica Chimica Acta; v. 484, p. 491-502, JAN 1 2019.
• Web of Science Citations: 1

Abstract

Polynuclear copper(II) complexes with nalidixic acid hydrazones derivatives containing 2-imidazolyl (h2imi, complexes 1A and 1B), 4-imidazolyl (h4imi, complexes 2A and 2B), salicyl (hsali, complex 3) and 1H-pyrrolyl (hpyrr, complex 4) units were synthesized and characterized by chemical and spectroscopic methods. Crystallographic studies of complex 1B, {[}Cu-3(h2imi(-))(2)Cl-4], show that coordination of hydrazones to Cu(II) occurs by tridentate modes of the type kappa(3)(O,N,N') as well as bidentate modes of the type kappa(2)(O',N `'). For complexes 2A and 4, EPR data are compatible with a trinuclear structure, based on an antiferromagnetic coupling between copper centers that is stronger at low temperature. Complexes 1A, 2A, 3 and 4 had their antiproliferative activities evaluated in vitro against a panel of tumor cells by determination of GI(50 )values. Complexes 3 (GI(50) = 1.14 mu M, SI = 4.52) and 4 (GI(50) = 2.72 mu M, SI = 6.06) were more active and selective against 786-0 cell lines than doxorubicin (GI(50) = 85.0 mu M, SI = 5.10(-3)). Complex 1A presented high selectivity indexes against glioma (U251, GI(50) = 2.53 mu M, SI = 60.9) and multiple drugs resistance ovarian (NCl/ADR-RES GI(50) = 1.69 mu M, SI = 91.4) cell lines when compared to doxorubicin and cisplatin. DNA gel electrophoresis (pIRES DNA) and cell-cycle arrest (NCl/ ADR-RES cell line) assays were performed with complex 1A. The obtained results suggest that the mechanism of action of complex 1A does not involve DNA interaction and complex 1A seems to be a cell cycle non-specific drug. (AU)

• 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