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Cellular Accumulation, Lipophilicity and Photocytotoxicity of Diazido Platinum(IV) Anticancer Complexes
Author(s) -
Pizarro Ana M.,
McQuitty Ruth J.,
Mackay Fiona S.,
Zhao Yao,
Woods Julie A.,
Sadler Peter J.
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201402066
Subject(s) - lipophilicity , chemistry , partition coefficient , platinum , prodrug , stereochemistry , medicinal chemistry , biochemistry , chromatography , catalysis
The lipophilicity of ten photoactivatable platinum(IV) diazido prodrugs of formula trans,trans,trans ‐[Pt(N 3 ) 2 (OH) 2 (R)(R′)] (where R and R′ are NH 3 , methylamine, ethylamine, pyridine, 2‐picoline, 3‐picoline or thiazole) has been determined by their retention times on reversed‐phase HPLC. The lipophilicity of the complexes shows a linear dependence on the lipophilicity (partition coefficient) of the ligands. Accumulation of platinum in A2780 human ovarian cancer cells after one hour drug exposure in the dark is compared with their cytotoxic potency on activation with UVA (365 nm) and to their lipophilicity. No correlation between lipophilicity and intracellular accumulation of platinum was observed, perhaps suggesting involvement of active transport and favoured influx of selected structures. Furthermore, no correlation between platinum accumulation and photocytotoxicity was observed in A2780 cancer cells, implying that the type of intracellular damage induced by these complexes plays a key role in their cytotoxic effects.