In vitro and in silico assessment of antitumor properties and biomolecular binding studies for two new complexes based on Ni-II bearing k(2)N, S-donor ligands

Author(s):Show less -

Farias, R. L. ^[1] ; Polez, A. M. R. ^[1] ; Silva, D. E. S. ^[1] ; Zanetti, R. D. ^[1] ; Moreira, M. B. ^{[1, 2]} ; Batista, V. S. ^[3] ; Reis, B. L. ^{[3, 4]} ; Nascimento-Junior, N. M. ^[3] ; Rocha, V, F. ; Lima, M. A. ^[5] ; Oliveira, A. B. ^[6] ; Ellena, J. ^[7] ; Scarim, C. B. ^[8] ; Zambom, C. R. ^[9] ; Brito, L. D. ^[9] ; Garrido, S. S. ^[9] ; Melo, A. P. L. ^[10] ; Bresolin, L. ^[10] ; Tirloni, B. ^[11] ; Pereira, J. C. M. ^[1] ; Netto, A. V. G. ^[1]

Affiliation:Show less -

^[1] Univ Estadual Paulista, UNESP, Inst Quim, Dept Quim Analit Fis Quim & Inorgan, Araraquara, SP - Brazil

^[2] Univ Estadual Londrina UEL, Dept Quim, Londrina, Parana - Brazil

^[3] Univ Estadual Paulista, UNESP, Inst Quim, Laboratario Quim Med Sintese Organ & Modelagem Mo, Araraquara, SP - Brazil

^[4] Tech Univ Dresden TUD, Dept Chem & Food Chem, Dresden - Germany

^[5] Rocha, F., V, Univ Fed Sao Carlos UFSCar, Dept Quim, Sao Carlos - Brazil

^[6] Univ Fed Sergipe UFS, Dept Quim, Sao Cristovao - Brazil

^[7] Univ Sao Paulo, Inst Fis Sao Carlos, Sao Carlos - Brazil

^[8] Univ Estadual Paulista, UNESP, Fac Ciencias Farmaceut, Araraquara, SP - Brazil

^[9] Univ Estadual Paulista, UNESP, Inst Quim, Dept Bioquim & Quim Organ, Araraquara, SP - Brazil

^[10] Univ Fed Rio Grande FURG, Escola Quim & Alimentos, Rio Grande - Brazil

^[11] Univ Fed Santa Maria UFSM, Dept Quim, Santa Maria, RS - Brazil

• Document type: Journal article
• Source: Materials Science & Engineering C-Materials for Biological Applications; v. 121, FEB 2021.
• Web of Science Citations: 0

Abstract

This work deals with two new molecule-based materials, namely Ni-II-complexes of general formulae {[}Ni(L1)(2)] (Ni1) and {[}Ni(L2)(2)] (Ni2), where L1 = trans-cinnamaldehyde-N(4)-methyl thiosemicarbazone and L2 = transcinnamaldehyde-N(4)-ethyl thiosemicarbazone, as potential antitumor agents. Both compounds were characterized by elemental analysis, molar conductivity and spectroscopic techniques (FTIR and NMR). Their molecular structures were obtained by single-crystal X-ray diffraction analysis. Each one crystallizes in a monoclinic space group P 2(1)/c, also the asymmetric unit comprises of one Ni-II ion located on an inversion centre and one anionic ligand, which acts as a kappa N-2,S-donor affording a five-membered metallaring. The compounds were screened against two selected tumour cell lines (MCF-7 and A549) and non-tumour fibroblasts cell line (MRC-5) via MTT assays. In both tumour cells, all compounds exhibited higher cytotoxicity than the control drug (cisplatin). The IC50 values ranges of 3.70 - 41.37 mu M and 1.06 - 14.91 mu M were found for MCF-7 and A549, respectively. Importantly, all of them were less toxicity than cisplatin in MRC-5 with SI values ranged at 11.80 - 86.60. The red blood cell (RBC) assay revealed Ni2 as non-toxic due to its reduced haemolytic effect (0--9% at 1--10 mu M). The DNA binding was investigated through a combination of spectrophotometric absorption and emission titrations, electrophoresis, and circular dichroism experiments. As a result, these metal complexes were not able to strongly binding to DNA (K-b values similar to 10(4) mol L--1) but suggesting groove-binding interactions. The scavenging ability of them towards 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical was also evaluated in this work, but no important antioxidant behaviour was detected. Further, the interaction of Ni1 and Ni2 to human serum albumin (HSA) was explored by quenching of tryptophan emission, warfarin competitive assay, and molecular docking protocols. The HSA binding analyses indicated good affinity of both complexes to Sudlow site I (K-b values similar to 10(3) mol L-1). (AU)

• FAPESP's process: 18/00187-7 - Design, computational studies, synthesis and pharmacological evaluation of novel bioactive substances against nicotinic acetylcholine receptors alpha7 and alpha4beta2
• Grantee: Nailton Monteiro Do Nascimento Júnior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/12098-0 - Dinitrosyl complexes containing thiol and/or thiosemicarbazone : synthesis, characterization and treatment against cancer
• Grantee: José Clayston Melo Pereira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/17711-5 - INVESTIGATION OF THE ANTITUMOR POTENTIAL OF PALLADIUM(II) COMPOUNDS CONTAINING ORTHOMETALLATED OR N,S-DONOR LIGANDS
• Grantee: Adelino Vieira de Godoy Netto
• Support Opportunities: Regular Research Grants