Theoretical Investigations and Density Functional Theory Based Quantitative Structure-Activity Relationships Model for Novel Cytotoxic Platinum(IV) Complexes
- Author(s)
- Hristo Varbanov, Michael Jakupec, Alexander Roller, Frank Jensen, Mathea Sophia Galanski, Bernhard Keppler
- Abstract
Octahedral platinum(IV) complexes are promising candidates in the fight against cancer. In order to rationalize the further development of this class of compounds, detailed studies on their mechanisms of action, toxicity, and resistance must be provided and structure activity relationships must be drawn. Herein, we report on theoretical and QSAR investigations of a series of 53 novel bis-, tins-, and tetrakis(carboxylato)platinum(IV) complexes, synthesized and tested for cytotoxicity in our laboratories. The hybrid DFT functional wb97x was used for optimization of the structure geometry and calculation of the descriptors. Reliable and robust QSAR models with good explanatory and predictive properties were obtained for both the cisplatin sensitive cell line CH1 and the intrinsically cisplatin resistant cell line SW480, with a set of four descriptors.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Aarhus University
- Journal
- Journal of Medicinal Chemistry
- Volume
- 56
- Pages
- 330-344
- No. of pages
- 15
- ISSN
- 0022-2623
- DOI
- https://doi.org/10.1021/jm3016427
- Publication date
- 2013
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 301305 Medical chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/47242bf0-88f9-4985-8cd3-b88a21ff1d6a