Phenanthroline complexation enhances the activity of the VOchrysin system

ACTIS DATO, A.; L. NASO; REY M.; GONZÁLEZ, P.; E.G. FERRER; P.A.M. WILLIAMS

Cyrus

Simposio; 12th International Vanadium Symposium, V12; 2021

University of Cyprus

Metal-based drugs development is a promising strategy for the enhancement of the pharmacological action of drugs. In particular, vanadium complexes have been recognized to display biological activities for the treatment of malignancies such as diabetes, cancer, tuberculosis, and leishmaniasis.1We have previously studied the anticancer behavior of chrysin and chrysin oxidovanadium(IV) metal complex, [VO(Chrys)2EtOH]2 (1), on osteoblast-like cells2 and showed that complexation enhanced the biological effects of the polyphenol. The selection of the heterocyclic base phenanthroline, as a second ligand, is related to the fact that planar ligands coordinated to metals could bind DNA through intercalation to base pairs, improving the anticancer action of binary complexes, and can also confer lipophilicity to the compounds.3 In the current work, we designed the heteroleptic VO-chrys-phen ternary complex, (2) [VO(Chrys)phenCl], aiming to enhance the anticancer action of the binary compound. The complex was characterized in the solid-state and in solution. Electronic and diffuse reflectance spectra showed the typical blue shift due to the different coordination spheres (4O (1) and 2O,2N (2)); ligand replacement produced a decrease of pi-electron donation to the V=O moiety (the shift of the V=O stretching band from 968 cm-1 (1) to 957 cm-1 (2) is indicative of a decrease of the bond order and an increase of the bond length). The spin Hamiltonian parameters and the hyperfine coupling constants in frozen DMSO were gII = 1.941; AII = 162.2 x 10-4 cm-1; g = 1.977; A = 59.5 x 10-4 cm-1 and fit well in the corresponding gII vs. AII diagram for a 2N,2O coordination sphere.4 The electronic spectra of a DMSO solution of (2) and the conductivity measurements (0.011 Ω−1cm2 mol-1) did not show any significant change during 4 h (data not shown) indicating that the complex remained stable during the preparative for the biological studies. The biological activity as an anticancer drug (cell viability at different incubation times and oxidative stress, 24 h incubation) was studied in a human lung cancer cell line A549. Data has been compared with the effects of the binary complex, the metal ion, and the ligands and will be discussed in the presentation. To discard complex hydrolysis inside the cells during 24 h incubation, cell viability of the VO + chrys + phen system was also measured