Arene Variation of Highly Cytotoxic Tridentate Naphthoquinone-Based Ruthenium(II) Complexes and In-Depth In Vitro Studies

Author(s)

Klaudia Cseh, Heiko Geisler, Kristina Stanojkovska, Julia Westermayr, Philipp Brunmayr, Dominik Wenisch, Natalie Gajic, Michaela Hejl, Martin Schaier, Gunda Koellensperger, Michael A. A. Jakupec, Philipp Marquetand, Wolfgang Kandioller

Abstract

The main purpose of this study was to synthesize a new set of naphthoquinone-based ruthenium(II) arene complexes and to develop an understanding of their mode of action. This study systematically reviews the steps of synthesis, aiming to provide a simplified approach using microwave irradiation. The chemical structures and the physicochemical properties of this novel group of compounds were examined by

¹H-NMR and

¹³C-NMR spectroscopy, X-ray diffractometry, HPLC-MS and supporting DFT calculations. Several aspects of the biological activity were investigated in vitro, including short- and long-term cytotoxicity tests, cellular accumulation studies, detection of reactive oxygen species generation, apoptosis induction and NAD(P)H:quinone oxidoreductase 1 (NQO1) activity as well as cell cycle analysis in A549, CH1/PA-1, and SW480 cancer cells. Furthermore, the DNA interaction ability was studied in a cell-free assay. A positive correlation was found between cytotoxicity, lipophilicity and cellular accumulation of the tested complexes, and the results offer some important insights into the effects of the arene. The most obvious finding to emerge from this study is that the usually very chemosensitive CH1/PA-1 teratocarcinoma cells showed resistance to these phthiocol-based organometallics in comparison to the usually less chemosensitive SW480 colon carcinoma cells, which pilot experiments suggest as being related to NQO1 activity.

Organisation(s)

Department of Inorganic Chemistry, Department of Analytical Chemistry, Department of Theoretical Chemistry, Research Platform Accelerating Photoreaction Discovery

External organisation(s)

Universität Leipzig, Vienna Doctoral School in Chemistry (DoSChem)

Journal

Pharmaceutics

Volume

14

No. of pages

22

DOI

https://doi.org/10.3390/pharmaceutics14112466

Publication date

11-2022

Peer reviewed

Yes

Austrian Fields of Science 2012

104003 Inorganic chemistry, 301209 Pharmacy, 301208 Pharmaceutical technology

Keywords

ASJC Scopus subject areas

Pharmaceutical Science

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Portal url

https://ucrisportal.univie.ac.at/en/publications/arene-variation-of-highly-cytotoxic-tridentate-naphthoquinonebased-rutheniumii-complexes-and-indepth-in-vitro-studies(887ab99b-7905-450d-99c5-5477efc68d00).html