A series of mononuclear Co(III) complexes using tridentate N,O-donor ligands: Chemical properties and cytotoxicity activity

• Published in: Journal of inorganic biochemistry 2011-12, Vol.105 (12), p.1767-1773
• Main Authors: Souza, Elizabeth Teixeira, Maia, Paulo José Sousa, Azevedo, Érica Melo, Kaiser, Carlos Roland, Resende, Jackson Antônio Lamounier Camargos, Pinheiro, Carlos Basílio, Heinrich, Tassiele Andrea, da Silva, Roberto Santana, Scarpellini, Marciela
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; B16F10; Cell Line, Tumor; Cell Survival - drug effects; Cobalt; Cobalt complexes; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Crystallography, X-Ray; Drug Screening Assays, Antitumor; Electrochemistry; Hypoxia; Inhibitory Concentration 50; Melanoma; Mice; Models, Molecular; Molecular Conformation; Oxidation-Reduction; Prodrugs
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2011.09.011

Continuing our interest in tridentate ligands to develop new prototypes of cobalt-based metallodrugs for combating cancer, modifications in the backbone of HL1, [(2-hydroxybenzyl)(2-(pyridil-2-yl)ethyl]amine) were proposed in order to modulate the redox potential of new Co(III) complexes. Three ligands with electron withdrawing groups were synthesized: HL2: [(2-hydroxy-5-nitrobenzyl)(2-(pyridil-2-yl)ethyl]amine); HL3: [(2-hydroxybenzyl)(2-(pyridil-2-yl)ethyl]imine) and HL4: [(2-hydroxy-5-nitrobenzyl)(2-(pyridil-2-yl)ethyl]imine). They were used to obtain the respective mononuclear complexes 2, 3 and 4, which are discussed compared to the previous reported complex 1 (obtained from HL1). The new complexes were characterized and studied by several techniques including X-ray crystallography, elemental and conductimetric analysis, IR, UV–vis and 1H NMR spectroscopies, and electrochemistry. The substitutions of the group in the para position of the phenol ( HL1 and HL2) and the imine instead of the amine ( HL3 and HL4), promote anodic shifts in the complexes reduction potentials. The influence of these substitutions in the biological activities of the Co(III) complexes against the murine melanoma cell line ( B16F10) was also evaluated. Little effect was observed on cellular viability decrease for all free ligands, however the coordination to Co(III) enhances their activities in the following range: 1 > 4 ≈ 2 > 3. The data suggest that no straight correlation can be addressed between the reduction potential of the Co(III) center and the cell viability. Three novel Co(III) complexes were synthesized and characterized to develop new metallodrugs to fight cancer. The Co(III) reduction potentials were modulated by electron-withdrawing groups in the backbone of tridentante N,O-donor ligands. The biological activities were evaluated against melanoma murine cell line (B16F10) with IC 50 values ranging from 60 to 125 μM. [Display omitted]