EN
3-Hydroxyflavones belong to the naturally
occurring class of flavonoids and have been extensively
studied with regard to medicinal application. Moreover,
it has been demonstrated that these compounds
act as bioactive chelates to the ruthenium(II)–arene
moiety. Such organometallic complexes have shown
promising anticancer activity against tumor cells via a
multitargeting mode of action, interacting with DNA and
inhibiting topoisomerase IIα. In this paper, we present
the synthesis and characterization of an extended series
of 3-hydroxyflavone ligands and their corresponding
ruthenium-p-cymene complexes to study the impact of
substitution pattern as well as of electron-withdrawing
and –donating substituents at the flavonol-phenyl
group. The ligands and complexes were characterized
by elemental analysis, ESI-MS, 1D as well as 2D NMR
spectroscopy. The structures of four Ru(η6-p-cymene)
complexes were determined in solid state by single-crystal
X-ray diffraction, and the impact of the substitution
pattern with regard to in vitro anticancer activity in human
cancer cell lines is discussed. Structural differences,
calculated octanol-water partition coefficients (clogP)
of the flavonols and aqueous solubility were used to
rationalize the finding that chlorido[3-(oxo-κO)-2-(3,5-
dimethoxyphenyl)-chromen-4-onato-κO](η6-p-cymene)ruthenium(II) 2b exhibits the highest cytotoxicity with
IC50 values in the low μM range in all tested cell lines.