Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 56, Issue 1, Pages 357-370Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm301691s
Keywords
-
Categories
Funding
- National Health and Medical Research Council
- Australian Research Council [DP0773027, DP1096029]
- Cancer Institute NSW [08/ECF/1-30]
- Australian Postgraduate Award from the University of Sydney
- Australian Research Council [DP0773027, DP1096029] Funding Source: Australian Research Council
Ask authors/readers for more resources
Thiosemicarbazone chelators, including the 2'-benzoylpyridine thiosemicarbazones (BpT) class, show marked potential as anticancer agents. Importantly, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) has been investigated in >20 phase I and II clinical trials. However, side effects associated with 3-AP administration include methemoglobinemia. Considering this problem, novel BpT analogues were designed bearing hydrophobic, electron-donating substituents at the para position of the phenyl group (RBpT). Their Fe-III/II redox potentials were all within the range accessible to cellular oxidants and reductants, suggesting they can redox cycle. These RBpT ligands exhibited potent and selective antiproliferative activity, which was comparable or exceeded their BpT counterparts. Major findings include that methemoglobin formation mediated by the lipophilic t-BuBpT series was significantly (p < 0.05-0.001) decreased in comparison to 3-AP in intact red blood cells and were generally comparable to the control. These data indicate the t-BuBpT ligands may minimize methemoglobinemia, which is a marked advantage over 3-AP and other potent thiosemicarbazones.
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