Exploring pta Alternatives in the Development of Ruthenium–Arene Anticancer Compounds
Jakob Kljun,
Mihaela Rebernik,
Lucía M. Balsa,
Jerneja Kladnik,
Uroš Rapuš,
Tomaž Trobec,
Kristina Sepčić,
Robert Frangež,
Ignacio E. León,
Iztok Turel
Affiliations
Jakob Kljun
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia
Mihaela Rebernik
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia
Lucía M. Balsa
CEQUINOR (UNLP, CCT-CONICET La Plata, Asociado a CIC), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Blvd. 120 N°1465, La Plata 1900, Argentina
Jerneja Kladnik
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia
Uroš Rapuš
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia
Tomaž Trobec
Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, SI-1000 Ljubljana, Slovenia
Kristina Sepčić
Department of Biology, Biotechnical Faculty, University of LjubljanaJamnikarjeva 101, SI-1000 Ljubljana, Slovenia
Robert Frangež
Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, SI-1000 Ljubljana, Slovenia
Ignacio E. León
CEQUINOR (UNLP, CCT-CONICET La Plata, Asociado a CIC), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Blvd. 120 N°1465, La Plata 1900, Argentina
Iztok Turel
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia
Organoruthenium pyrithione (1-hydroxypyridine-2-thione) complexes have been shown in our recent studies to be a promising family of compounds for development of new anticancer drugs. The complex [(η6-p-cymene)Ru(pyrithionato)(pta)]PF6 contains phosphine ligand pta (1,3,5-triaza-7-phosphaadamantane) as a functionality that improves the stability of the complex and its aqueous solubility. Here, we report our efforts to find pta alternatives and discover new structural elements to improve the biological properties of ruthenium anticancer drugs. The pta ligand was replaced by a selection of phosphine, phosphite, and arsine ligands to identify new functionalities, leading to improvement in inhibitory potency towards enzyme glutathione S-transferase. In addition, cytotoxicity in breast, bone, and colon cancers was investigated.
