Heteroleptic ruthenium bioflavonoid complexes: from synthesis to in vitro biological activity

Abstract

Heteroleptic ruthenium(II) bioflavonoid complexes of quercetin, morin, chrysin, and 3-hydroxyflavone were prepared and their interaction with CT DNA and BSA along with antioxidant and in vitro anticancer and antimicrobial activities was investigated. The formulation and characterization of complexes were achieved through elemental and thermal analysis, mass spectrometry, 1H NMR spectroscopy along with infrared, electronic absorption, and emission spectroscopy as well as square-wave voltammetry, and magnetic and conductivity measurements. Ruthenium(II) is octahedrally coordinated in cationic complex species to two bidentate diimine ligands (2,2′-bipyridine or 1,10-phenanthroline) and one bidentate monobasic flavonoid ligand through 3,4-site of quercetin, morin, and 3-hydroxyflavone or 4,5-site of chrysin. Complexes bind CT DNA by intercalation and binding constants comparable to ethidium bromide or 10 times higher. Binding constants of complexes to BSA were several times higher compared to ibuprofen and diazepam, and suggest that the complexes have a strong affinity to BSA. Antioxidant activity tests showed that the complexes are more potent in terms of radical inhibition compared to the parent flavonoids. Cytotoxic testing revealed that the Ru(II) complex of quercetin with 2,2′-bipyridine co-ligand has good selectivity to breast adenocarcinoma, while the complex of 3-hydroxyflavone with 2,2′-bipyridine co-ligand showed strong cytotoxicity toward all tested cell lines with IC50 ∼ 1 μM. All complexes showed moderate activity toward Acinetobacter baumannii, while the Ru(II) complex of 3-hydroxyflavone with 2,2′-bipyridine showed excellent activity toward MRSA and Candida albicans.