New Ru(II)-DMSO complexes containing coumarin-N-acylhydrazone hybrids: Synthesis, X-ray structures, cytotoxicity and antimicrobial activities

Four novel coumarin-N-acylhydrazone hybrid ligands HL2-5 [(E)-7-(diethylamino)-N'-(4-R-benzylidene)-2-oxo-2H-chromene-3-carbohydrazide, where R = H: HL2; CI: HL3; Br: HL4 and OCH3: HL5] were obtained from condensation reactions of HL1 (7-(diethylamino)-2-oxo-2H-chromene-3-carbohydrazide) and p-substituted aldehydes. The reactions of HL2-5 with cis-[RuCl 2 (DMSO)(4)] in ethanol resulted in the Ru(II) complexes C2-5 of the type trans-ClRuCl2(DMSO)(2)(HLn)]. Concomitantly, hydrolysis of the ligand occurred, affording complex Cl trans-Cl-[RuCl2(DMSO)(2)(HL1)]. X-ray diffraction analyses revealed E/Z isomerization of the coumarin-N-acylhydrazones upon coordinating with Ru(II). C2-5 exhibit the Ru(II) atom in a distorted octahedral geometry with the ligand HL coordinated in the keto form through the hydrazone carbonyl and the iminic nitrogen. Ligands (HL1-5) and Ru(II)-DMSO complexes (Cl-5) were screened for their antiproliferative activities. In general, the free ligands were more cytotoxic than the Ru(II) complexes, possibly caused by lower membrane permeation capacity of the latter and different mechanism of action than those displayed by the ligands. Amongst coumarin-N-acylhydrazone ligands, the highest potency of HL4 (IC50 = 16.1 and 11.9 mu M for 4T1 and B16-F10, respectively) was associated to its better lipophilicity, caused by a -Br substituent. Antimicrobial assays towards gram-positive and gram-negative strains showed that only HL1 and complexes C2-5 were soluble in the agar gel culture media. C4 (R = Br) was the most effective compound (MIC = 40.5 mu M for Staphylococcus aureus), also correlated to lipophilic parameters. (C) 2019 Elsevier Ltd. All rights reserved.