Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 52, Issue 2, Pages 407-415Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm801012z
Keywords
-
Categories
Funding
- Australian Research Council Discovery [DP0773027]
- National Health and Medical Research Council of Australia
- Cancer Institute NSW
- Australian Research Council [DP0773027] Funding Source: Australian Research Council
Ask authors/readers for more resources
We previously reported a series of di-2-pyridylketone thiosemicarbazone (HDpT) chelators that showed marked and selective antitumor activity (Whitnall, M.; et al. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 14901-14906). To further understand their biological efficacy, we report the characterization and activity of their Mn-II, Co-III, Ni-II, Cu-II, and Zn-II complexes. The X-ray crystal structures of four divalent (Mn, Ni, Cu, and Zn) and one trivalent (Fe) complexes are reported. Electrochemistry shows the Fe-III/II and Cu-II/I potentials of the complexes may be redox-active within cells. Stability constants were also determined for the Mn-II, Ni-II, Cu-II, and Zn-II complexes. All divalent complexes underwent transmetalation upon encountering Fe-II, to form low spin ferrous complexes. Importantly, the divalent Mn-II, Ni-II, Cu-II, and Zn-II complexes of the HDpT analogues are equally active in preventing proliferation as their ligands, suggesting the complexes act as lipophilic vehicles facilitating intracellular delivery of the free ligand upon metal dissociation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available