Tuning of lipophilicity and cytotoxic potency by structural variation of anticancer platinum(IV) complexes.
A series of bis(carboxylato)dichlorido(ethane-1,2-diamine)platinum(IV) compounds with IC(50) values ranging between 142 μM and 18 nM was investigated with respect to their lipophilicity (by the shake flask method as well as microemulsion electrokinetic chromatography), reduction potential, as well as their cellular accumulation in cancer cells in vitro. In general, the antiproliferative properties of the complexes correlated with their lipophilicity as well as their accumulation, whereas differences in antiproliferative potency could not be explained by reduction potentials since they do not vary significantly within the investigated series of compounds. Only minor effects for complexes featuring polar end groups were detected.
University of Vienna, Institute of Inorganic Chemistry, Waehringer Str. 42, A-1090 Vienna, Austria.
Michael R
MR
Reithofer
Anna K
AK
Bytzek
Seied M
SM
Valiahdi
Christian R
CR
Kowol
Michael
M
Groessl
Christian G
CG
Hartinger
Michael A
MA
Jakupec
Mathea S
MS
Galanski
Bernhard K
BK
Keppler
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004563:Electrochemistry; D006367:HeLa Cells; D006801:Humans; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds