Synthesis, crystal structure and cytotoxicity of new oxaliplatin analogues indicating that improvement of anticancer activity is still possible.
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.
Institute of Inorganic Chemistry, University of Vienna, Waehringerstr. 42, A-1090 Vienna, Austria. markus.galanski@univie.ac.at
Mathea S.
MS
Galanski
Afshin
A
Yasemi
Susanna
S
Slaby
Michael A
MA
Jakupec
Vladimir B
VB
Arion
Monika
M
Rausch
Alexey A
AA
Nazarov
Bernhard K
BK
Keppler
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D045744:Cell Line, Tumor; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D000077150:Oxaliplatin
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin