Synthesis and structure-activity relationships of mono- and dialkyl-substituted oxaliplatin derivatives
- Author(s)
- Ladislav Habala, Mathea Sophia Galanski, Afshin Yasemi, Alexey Nazarov, Nikolai Graf v. Keyserlingk, Bernhard Keppler
- Abstract
In order to improve the pharmacological profile of the anticancer drug oxaliplatin, (trans-R,R-cyclohexane-1,2-diamine)oxalatoplatinum(II), and to explore activity-structure relationships, new mono- and dialkyl substituted oxaliplatin analogues have been synthesized. Following a new synthetic strategy, racemates with a defined stereochemistry at carbon atoms 1, 2, 4, and 5 of the cyclohexane ring could be prepared, which are the bases for reliable structure-activity relationships and the following enantiomer resolution. The cytotoxicity was evaluated in nine tumor cell lines, indicating that bulky substituents have a negative influence on the cytotoxic potency of the oxaliplatin derivatives. With respect to the antiproliferative properties, the 4-methyl-, cis-4,5-dimethyl-, and especially the 4,4-dimethyl-trans-cyclohexane- 1,2-diamine(oxalato)platinum(II) complexes are the most promising candidates to be further evaluated. Π2005 Elsevier SAS. All rights reserved.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Faustus Forschungs Compagnie GmbH
- Journal
- European Journal of Medicinal Chemistry
- Volume
- 40
- Pages
- 1149-1155
- No. of pages
- 7
- ISSN
- 0223-5234
- Publication date
- 2005
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 1040 Chemistry
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/abb3292c-fcf3-4d38-ae76-1c905567917d