Development of biologically active metal complexes: synthesis, spectroscopy and biological evaluation of ruthenium-based benzimidazolium complexes against cancer

Ramulumo, Humbelani

Development of biologically active metal complexes: synthesis, spectroscopy and biological evaluation of ruthenium-based benzimidazolium complexes against cancer

Master Thesis

2023

Abstract

The study focused on the synthesis and characterisation of ionic imidazopyridine tetracarboxylato diruthenium complexes bearing different counterions like NO3, PF6 and BF4. The complexes were fully characterized using a variety of analytical techniques such as spectroscopy (1H, UV-Vis and FTIR) and cyclic voltammetry. Mass spectrometry was used to identify the masses of the products of interests to confirm the successful formation of new species. The biological activity of the synthesized complexes was evaluated against MCF-7 breast cancer cells as well as the non-tumorigenic MCF-12A epithelial cell lines. The stability of the solvents in DMSO at room temperature conditions was evaluated for a period of 72 h, and the complexes showed sufficient stability. All the synthesized complexes displayed significantly good anticancer activity against the MCF-7 breast cancer cell line. The complexes displayed good solubility in solvents like DMSO and biological media relative to the diruthenium tetraacetate chloride precursor complex and relative to the ligands. The resulting complexes displayed superior anticancer activity in comparison to the free uncoordinated ligands and this was comparable to that of the anticancer drug Cisplatin. Complexes bearing ligands with ferrocene displayed the best anticancer activity with IC50 values in the μM range and comparable to those of cisplatin. The complex C7 containing 2- ferrocenyl-1H-Imidazo(4,5-c)pyridine (L3) had the greatest anticancer activity (IC50 value of 66.47 μM) towards the MCF-7 breast cancer cell line while complex C5 containing the phenyl substituted ligand showed the lowest anticancer activity with an IC50 value of 79.58 μM. The selectivity indices (S.I.) of the complexes C5, C7 and C13 were also determined from the IC50 values of MCF-12A and MCF-7 breast cancer cells. Complex C5 was highly cytotoxic to the non-tumorigenic cell line at all tested concentrations and reduced the cell viability of MCF-12A cell line by more than 90% at maximum tested concentration. Complexes C7 and C13 displayed moderate cytotoxicity towards the healthy cell lines relative to cisplatin. The selectivity studies indicated that one of the compounds bearing a phenyl substituted ligand was toxic to the normal healthy cell line.

Keywords

Chemistry

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