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

doi:10.3390/molecules28062499

Molecules (Mar 2023)

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

DOI: https://doi.org/10.3390/molecules28062499
Journal volume & issue: Vol. 28, no. 6
p. 2499

Abstract

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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.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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