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doi:10.1016/j.ejmech.2004.04.003 
Copyright © 2004 Elsevier SAS. All rights reserved.
Original article
Synthesis, crystal structure and cytotoxicity of new oxaliplatin analogues indicating that improvement of anticancer activity is still possible
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Markus Galanski
, 
, Afshin Yasemi, Susanna Slaby, Michael A. Jakupec, Vladimir B. Arion, Monika Rausch, Alexey A. Nazarov and Bernhard K. Keppler
Received 24 November 2003;
Abstract
Oxaliplatin, (trans-R,R-cyclohexane-1,2-diamine)oxalatoplatinum(II), has recently been approved for combination chemotherapy of metastatic colorectal cancer. Oxaliplatin is significantly more active than its trans-S,S isomer and the mixture of both enantiomers. New oxaliplatin analogues, (SP-4-3)-(4-methyl-trans-cyclohexane-1,2-diamine)oxalatoplatinum(II) and (SP-4-3)-(4-ethyl-trans-cyclohexane-1,2-diamine)oxalatoplatinum(II), have been synthesized, and their cytotoxicity has been tested in comparison to oxaliplatin, its corresponding trans-S,S isomer, and the mixture of both enantiomers. In comparison to oxaliplatin, even the trans-R,R/trans-S,S mixture of the 4-methyl and 4-ethyl substituted oxaliplatin analogues have shown an equivalent cytotoxicity in ovarian cancer cells (CH1) and superior antiproliferative properties in colon cancer cells (SW480) in the case of a predominantly equatorial position of the substituent at position 4 of the trans-cyclohexane-1,2-diamine ligand, whereas an axial substitution results in decreased cytotoxic potency.
Author Keywords: Platinum; Anticancer complexes; Oxaliplatin; Synthesis; Crystal structure; Cytotoxic activity
Article Outline
- 1. Introduction
- 2. Results and discussion
- 3. Conclusions
- 4. Experimental
- 4.1. Syntheses
- 4.1.1. Synthesis of trans-cyclohexane-1,2-diamine dihydrogensulfates
- 4.1.1.1. Method A
- 4.1.1.1.1. 4-Methyl-trans-cyclohexane-1,2-diamine dihydrogensulfate
- 4.1.1.1.2. 4-Ethyl-trans-cyclohexane-1,2-diamine dihydrogensulfate
- 4.1.1.2. Method B
- 4.1.2. 4-Methyl-cis-cyclohexane-1,2-diamine dihydrogensulfate
- 4.1.3. Synthesis of dichloroplatinum complexes
- 4.1.3.1. (SP-4-3)-Dichloro(4-methyl-trans-cyclohexane-1,2-diamine)platinum(II)
- 4.1.3.2. (SP-4-3)-Dichloro(4-ethyl-trans-cyclohexane-1,2-diamine)platinum(II)
- 4.1.3.3. (SP-4-3)-Dichloro(4-methyl-trans-cyclohexane-1,2-diamine)platinum(II)
- 4.1.3.4. (SP-4-3)-Dichloro(4-ethyl-trans-cyclohexane-1,2-diamine)platinum(II)
- 4.1.4. Synthesis of oxalatoplatinum complexes
- 4.1.4.1. (SP-4-3)-(4-Methyl-trans-cyclohexane-1,2-diamine)oxalatoplatinum(II), rac-1(eq/ax)
- 4.1.4.2. (SP-4-3)-(4-Ethyl-trans-cyclohexane-1,2-diamine)oxalatoplatinum(II), rac-2(eq/ax)
- 4.1.4.3. (SP-4-3)-(4-Methyl-trans-cyclohexane-1,2-diamine)oxalatoplatinum(II), rac-1(eq/ax)
- 4.1.4.4. (SP-4-3)-(4-Ethyl-trans-cyclohexane-1,2-diamine)oxalatoplatinum(II), rac-2(eq/ax)
- 4.2. Physical measurements
- 4.3. Structure determination
- 4.4. Cell lines and culture conditions
- 4.5. Cytotocicity tests in cancer cell lines
- 5. Supplementary material
- Acknowledgements
- References
