Synthesis, Characterization, and Antitumor Activity of Water-Soluble (Arene)ruthenium(II) Derivatives of 1,3-Dimethyl-4-acylpyrazolon-5-ato Ligands. First Example of Ru(arene)(ligand) Antitumor Species Involving Simultaneous Ru–N7(guanine) Bonding and Ligand Intercalation to DNA

We
report on the synthesis of novel water-soluble [(arene)­RuII(Q)­Cl] and [(arene)­RuII(Q)­(X)]­BF4 compounds
(arene = p-cymene, benzene, hexamethylbenzene; HQ
= 1,3-dimethyl-4-R-(CO)-5-pyrazolone, HQMe, R =
methyl, HQPh, R = phenyl, HQNaph, R = naphthyl;
X = H2O, 9-ethylguanine), and their in vitro antitumor activity toward the cell lines MCF7 (HTB-22, human breast
adenocarcinoma), HCT116 (CCL-247, human colorectal carcinoma), A2780
(human ovarian carcinoma), A549 (CCL-185, human lung carcinoma), and
U87 MG (HTB-1, human glioblastoma). The X-ray crystal structures of
two complexes were determined. One of them, {chlorido-(p-cymene)-[(1,3-dimethyl-4-(1-naphthoyl)-pyrazolon-5-ato]­ruthenium­(II)},
was also studied with density functional theory methods and was selected
for docking on a DNA octamer showing intercalation between DNA bases
by the naphthyl moiety and for Ru–N7­(guanine) bonding.