Synthesis, crystal structure and cytotoxicity of new oxaliplatin analogues indicating that improvement of anticancer activity is still possible

• Published in: European journal of medicinal chemistry Vol. 39; no. 8; pp. 707 - 714
• Main Authors: Galanski, Mathea S., Yasemi, Afshin, Slaby, Susanna, Jakupec, Michael A., Arion, Vladimir B., Rausch, Monika, Nazarov, Alexey A., Keppler, Bernhard K.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Masson SAS 01-08-2004; Elsevier
• Subjects: Anticancer complexes; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - toxicity; Biological and medical sciences; Cell Line, Tumor; Crystal structure; Crystallization; Cytotoxic activity; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor - methods; General aspects; Humans; Medical sciences; Organoplatinum Compounds - chemical synthesis; Organoplatinum Compounds - chemistry; Organoplatinum Compounds - toxicity; Oxaliplatin; Pharmacology. Drug treatments; Platinum; Synthesis; Oxaliplatin; Synthesis; Platinum; Anticancer complexes; Crystal structure; Cytotoxic activity; Antineoplastic agent; Divalent metal Complexes; Oxalate; Cytotoxicity; Ovary; Racemic; Synthesis: Crystal structure; Structure activity relation; Trans stereoisomer; Colon; Chemical synthesis; Tumor cell; Platinum II Complexes; Human; Organic ligand; Transition metal Complexes; X ray diffraction; In vitro; Diamine; Cell line; Carboxylate; Crystalline structure
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2004.04.003

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.