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Cytotoxicity, hydrophobicity, uptake, and distribution of osmium(II) anticancer complexes in ovarian cancer cells
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van Rijt, Sabine H., Mukherjee, Arindam, Pizarro, Ana M. and Sadler, P. J.. (2010) Cytotoxicity, hydrophobicity, uptake, and distribution of osmium(II) anticancer complexes in ovarian cancer cells. Journal of Medicinal Chemistry, Vol.53 (No.2). pp. 840-849. ISSN 0022-2623
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Official URL: http://dx.doi.org/10.1021/jm901556u
Abstract
The cytotoxicity, hydrophobicity (log P), cellular uptake, aqueous reactivity, and extent of DNA adduct formation in the A2780 ovarian carcinoma cells for four osmium(II) arene complexes [(eta(6)-arene)Os(4-methyl-picolinate)CI] that differ only in their arene ligands as benzene (1),p-cymene (2), biphenyl (3), or tetrahydroanthracene (4) are reported. There is a correlation between hydrophobicity (log P), cellular uptake, nucleus uptake, and cytotoxicity of the complexes, following the order 3 similar to 4 > 2 > 1, suggesting that the arene plays an important role in the biological activity of these types of compounds. Cell distribution studies using fractionation showed that all four compounds distribute similarly within cells. DNA binding of osmium did not correlate with cytotoxicity, indicating that the nature of the DNA lesion may also be crucial to activity. TEM images of ovarian cells treated with 3 revealed morphological changes associated with apoptosis with possible involvement of mitochondria.
| Item Type: | Journal Article |
|---|---|
| Subjects: | Q Science > QD Chemistry R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | Faculty of Science > Chemistry |
| Library of Congress Subject Headings (LCSH): | Cell-mediated cytotoxicity, Osmium compounds, Antineoplastic agents, Cancer cells, Ovaries -- Cancer -- Molecular aspects -- Research |
| Journal or Publication Title: | Journal of Medicinal Chemistry |
| Publisher: | American Chemical Society |
| ISSN: | 0022-2623 |
| Date: | 28 January 2010 |
| Volume: | Vol.53 |
| Number: | No.2 |
| Number of Pages: | 10 |
| Page Range: | pp. 840-849 |
| Identification Number: | 10.1021/jm901556u |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Restricted or Subscription Access |
| Funder: | European Commission (EC), Medical Research Council (Great Britain) (MRC), Advantage West Midlands (AWM), European Regional Development Fund (ERDF) |
| Grant number: | G0701062 (MRC) |
| URI: | http://wrap.warwick.ac.uk/id/eprint/16588 |
Data sourced from Thomson Reuters' Web of Knowledge
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