Molecules, Vol. 28, Pages 2499: Exploring pta Alternatives in the Development of Ruthenium–Arene Anticancer Compounds

Molecules, Vol. 28, Pages 2499: Exploring pta Alternatives in the Development of Ruthenium–Arene Anticancer Compounds

Molecules doi: 10.3390/molecules28062499

Authors: Jakob Kljun Mihaela Rebernik Lucía M. Balsa Jerneja Kladnik Uroš Rapuš Tomaž Trobec Kristina Sepčić Robert Frangež Ignacio E. León Iztok Turel

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.