1,3-Dioxoindan-2-carboxamides as Bioactive Ligand Scaffolds for the Development of Novel Organometallic Anticancer Drugs
- Author(s)
- Stephan Mokesch, Maria S. Novak, Alexander Roller, Michael A. Jakupec, Wolfgang Kandioller, Bernhard K. Keppler
- Abstract
A series of novel 1,3-dioxoindan-2-carboxamide-based complexes were synthesized, designed to employ both the attributes of half-sandwich complexes and the topoisomerase inhibiting properties of the ligand scaffold. The compounds were characterized with standard analytical methods. Their stability in aqueous systems and the impact of either the metal center or the ligand scaffold on the affinity toward small biomolecules such as amino acids, DNA model compounds, and small proteins were determined by IT-ESI mass spectrometry. The cytotoxicity was investigated in three human cancer cell lines by means of a colorimetric MTT assay, and preliminary structure-activity relationships were derived. The benzyl derivatives showed the highest in vitro activity and promising topoisomerase IIα inhibition in the range of the IC
50 values. In addition, the induced changes in the cell cycle distribution were determined and the apoptosis induction potential elucidated.
- Organisation(s)
- Department of Inorganic Chemistry, Core Facility Crystal Structure Analysis
- Journal
- Organometallics
- Volume
- 34
- Pages
- 848-857
- No. of pages
- 10
- ISSN
- 0276-7333
- DOI
- https://doi.org/10.1021/om501032s
- Publication date
- 03-2015
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 104015 Organic chemistry, 301904 Cancer research
- Keywords
- ASJC Scopus subject areas
- Inorganic Chemistry, Physical and Theoretical Chemistry, Organic Chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/c6d118fe-ae71-4655-9d67-7503d673b217