Margiotta, Nicola, Marzano, Cristina, Gandin, Valentina, Osella, Domenico, Ravera, Mauro, Gabano, Elisabetta, Platts, James Alexis  ORCID: https://orcid.org/0000-0002-1008-6595, Petruzzella, Emanuele, Hoeschele, James D. and Natile, Giovanni
2012.
Revisiting [PtCl2(cis-1,4-DACH)]: an underestimated antitumor drug with potential application to the treatment of oxaliplatin-refractory colorectal cancer.
Journal of Medicinal Chemistry
55
(16)
, pp. 7182-7192.
10.1021/jm3006838
|
Abstract
Although the encouraging antitumor activity of [PtCl2(cis-1,4-DACH)] (1; DACH = diaminocyclohexane) was shown in early studies almost 20 years ago, the compound has remained nearly neglected. In contrast, oxaliplatin, containing isomeric 1R,2R-DACH carrier ligand, enjoys worldwide clinic application as a most important therapeutic agent in the treatment of colorectal cancer. By extending the investigation to human chemo-resistant cancer cells, we have demonstrated the real effectiveness of 1 in circumventing cisplatin and oxaliplatin resistance in LoVo colon cancer cells. The uptake of compound 1 by the latter cells was similar to that of sensitive LoVo cells. This is not the case for all other compounds considered in this investigation. Interaction with ds-DNA, investigated by a biosensor assay and by QM/MM geometry optimization of the 1,2-GG intrastrand cross-link, does not show significant differences between 1 and oxaliplatin. However, the DNA adducts of 1 are removed from repair systems with lower efficiency and are more effective in inhibiting DNA and RNA polymerase.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Professional Services > Advanced Research Computing @ Cardiff (ARCCA) Schools > Chemistry |
| Subjects: | Q Science > QD Chemistry |
| Publisher: | American Chemical Society |
| ISSN: | 0022-2623 |
| Last Modified: | 21 Oct 2022 08:57 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/34873 |
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