Synthesis and structural characterization of a series of ternary copper(II)-L-dipeptide-neocuproine complexes. Study of their cytotoxicity against cancer cells including MDA-MB-231, triple negative breast cancer cells

Author(s)

Alvarez, Natalia ^[1] ; Vina, Diana ^[1] ; Leite, Celisnolia M. ^[2] ; Mendes, Luis F. S. ^[3] ; Batista, Alzir A. ^[2] ; Ellena, Javier ^[4] ; Costa-Filho, Antonio J. ^[3] ; Facchin, Gianella ^[1]

Affiliation

^[1] Univ Republica, Fac Quim, Av Gen Flores 2124, Montevideo - Uruguay

^[2] Univ Fed Sao Carlos, Dept Quim, CP 676, BR-13565905 Sao Carlos, SP - Brazil

^[3] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Av Bandeirantes, BR-14040901 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Inst Fis Sao Carlos, CP 369, BR-13560970 Sao Carlos, SP - Brazil

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 203, FEB 2020.
• Web of Science Citations: 0

Abstract

This work presents the synthesis and characterization of eight copper complexes {[}Cu(L-dipeptide)(neo)]center dot nH(2)O (neo = neocuproine) and their cytotoxic activities against tumor cell lines. The crystalline structure of {[}Cu(gly-val)(neo)]center dot 3H(2)O, {[}Cu(gly-leu)(neo)]center dot H2O, {[}Cu(ala-gly)(neo)]center dot 4H(2)O, {[}Cu(val-phe)(neo)]center dot 4.5H(2)O and {[}Cu(phephe)(neo)]center dot 3H(2)O were determined by single crystal X-ray diffraction. In all of them, the Cu(II) is pentacoordinated, in a square pyramidal environment. The coordination observed in solid state was retained in the major species in aqueous solution, as suggested by Electronic Paramagnet Resonance and UV-vis spectroscopies. The complexes were shown to have affinity for isolated DNA, as determined by Circular Dichroism experiments. Furthermore, biological experiments showed that all the complexes present high cytotoxic activity against the cell lines: MDA-MB-231, MCF-7 (human metastatic breast adenocarcinomas, the first triple negative), MCF-10A (human normal breast cells), A549 (human lung epithelial carcinoma) and MRC-5 (human lung epithelial cells). Together, these results suggest that these compounds are promising steps towards new effective drugs to treat cancer. (AU)

• FAPESP's process: 15/50366-7 - Resolving mechanistic details of peptide transport across membranes using crystallographic and non-crystallographic structural biology approaches
• Grantee: Antonio José da Costa Filho
• Support type: Regular Research Grants
• FAPESP's process: 17/24669-8 - Unraveling the molecular bases of the early protein secretory pathway in humans using biophysical techniques
• Grantee: Luis Felipe Santos Mendes
• Support type: Scholarships in Brazil - Post-Doctorate