Nitric oxide donating furoxan derivatives and ruthenium(II) complexes as anticancer and antibacterial agents

Ruthenium(II)-arene complexes were combined with furoxan (1,2,5-oxadiazole 2-oxide) moieties to generate new anticancer and antibacterial drug candidates. Previous studies have shown that Ru(II) organometallic complexes can exhibit significant anticancer activity with low levels of side-effects. Furoxans are heterocyclic molecules capable of releasing nitric oxide (NO), which can induce apoptosis or necrosis. Therefore, furoxans were employed as ligands for Ru(II)-arene complexes to design new drug candidates. Furoxan derivatives were synthesized with different substituents (-NO2, -H, -OCH3, -OPh, -SPh, -SOPh, -SO2Ph), which were found to affect the amount of NO released. NO release was quantified via electron paramagnetic resonance (EPR) spectroscopy. The complexes were found to donate more NO than the ligands; the highest concentration of NO was donated by the complex containing (-SO2Ph) substituent. Furthermore, antibacterial assays were performed, and the complexes exhibited higher cytotoxicity than the corresponding ligands. This work also reports the synthesis of a new heterobimetallic complex combining a Ru(II)-arene with a gold(III) compound.