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Cellular Accumulation, Lipophilicity and Photocytotoxicity of Diazido Platinum(IV) Anticancer Complexes

Pizarro, Ana M. ; McQuitty, Ruth J. ; Mackay, Fiona S. ; Zhao, Yao ; Woods, Julie A. ; Sadler, Peter J.

ChemMedChem, 2014-06, Vol.9 (6), p.1169-1175 [Periódico revisado por pares]

Weinheim: WILEY-VCH Verlag

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Título:
Cellular Accumulation, Lipophilicity and Photocytotoxicity of Diazido Platinum(IV) Anticancer Complexes
Autor: Pizarro, Ana M. ; McQuitty, Ruth J. ; Mackay, Fiona S. ; Zhao, Yao ; Woods, Julie A. ; Sadler, Peter J.
Assuntos: Amines - chemistry ; anticancer agents ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - metabolism ; Antineoplastic Agents - toxicity ; Cell Line, Tumor ; Cell Survival - drug effects ; Cell Survival - radiation effects ; cell uptake ; Chromatography, High Pressure Liquid ; Cisplatin - chemistry ; Cisplatin - toxicity ; Coordination Complexes - chemistry ; Coordination Complexes - metabolism ; Coordination Complexes - toxicity ; Cytotoxicity ; Humans ; Isomerism ; lipophilicity ; Medical research ; metallodrugs ; Ovarian cancer ; photocytotoxicity ; Picolines - chemistry ; Platinum ; Platinum - chemistry ; platinum drugs ; Thiazoles - chemistry ; Ultraviolet Rays
É parte de: ChemMedChem, 2014-06, Vol.9 (6), p.1169-1175
Notas: istex:1100722E4ECD94FCC48324B52F4B2748A6AB3B3C
Spanish Ministry of Economy and Competitiveness - No. RYC-2012-11231
ArticleID:CMDC201402066
EC FP7-PEOPLE-2011-COFUND "AMAROUT II" program
ark:/67375/WNG-G8343LH5-Z
UK Engineering and Physical Sciences Research Council (EPSRC)
Science City Research Alliance
European Research Council (ERC) - No. 247450
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: The lipophilicity of ten photoactivatable platinum(IV) diazido prodrugs of formula trans,trans,trans‐[Pt(N3)2(OH)2(R)(R′)] (where R and R′ are NH3, 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. A spotlight on structure–activity: We have determined the lipophilicity (by HPLC) and accumulation of Pt in human ovarian cancer cells for a series of ten photoactivatable platinum(IV) diazido complexes. Lack of correlation indicates the possible involvement of active membrane transport. Accumulation does not correlate with photocytotoxicy, highlighting the importance of other factors such as photoactivation efficiency and nature of the photoproducts.
Editor: Weinheim: WILEY-VCH Verlag
Idioma: Inglês;Alemão

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Cellular Accumulation, Lipophilicity and Photocytotoxicity of Diazido Platinum(IV) Anticancer Complexes

Pizarro, Ana M. ; McQuitty, Ruth J. ; Mackay, Fiona S. ; Zhao, Yao ; Woods, Julie A. ; Sadler, Peter J.

Weinheim: WILEY-VCH Verlag

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