| Abstract
| - There has been much interest in the development of iron (Fe) chelators for the treatment of cancer. Wedeveloped a series of di-2-pyridyl ketone thiosemicarbazone (HDpT) ligands which show marked and selectiveantitumor activity in vitro and in vivo. In this study, we assessed chemical and biological properties ofthese ligands and their Fe complexes in order to understand their marked activity. This included examinationof their solution chemistry, electrochemistry, ability to mediate redox reactions, and antiproliferative activityagainst tumor cells. The higher antiproliferative efficacy of the HDpT series of chelators relative to therelated di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) analogues can be ascribed, in part, to theredox potentials of their Fe complexes which lead to the generation of reactive oxygen species. The mosteffective HDpT ligands as antiproliferative agents possess considerable lipophilicity and were shown to becharge neutral at physiological pH, allowing access to intracellular Fe pools.
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