Disulfide-masked pro-chelator compositions and methods of use
AssigneeArizona Board of Regents on Behalf of the University of Arizona
InventorsElisa Tomat, Eman A. Akam
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Abstract
Pro-chelator compositions featuring disulfide masks that upon activation yield active chelators. The pro-chelator compositions may be activated intracellularly, for example within cells featuring metal ion dysregulation, cells that proliferate abnormally, etc. The pro-chelators of the present invention include thiosemicarbazones, semicarbazones, and aroyl hydrazones. The pro-chelator compositions of the present invention may be used for a variety of purposes including inhibiting cell proliferation, or treating conditions associated with metal ion dysregulation or abnormal cell proliferation.
Claims20
A pro-chelator comprising at least one pro-ligand and a disulfide bond, wherein the disulfide bond is connected to the pro-ligand, and wherein each pro-ligand comprises at least two donor atoms.
A method of preventing iron-deficiency anemia while treating a subject having malignant cells characterized by a reprogrammed iron metabolism, the method comprising:
- a. providing a pro-chelator to a bloodstream of the subject, the pro-chelator comprising at least one pro-ligand and a disulfide bond, wherein the disulfide bond is connected to the pro-ligands, and wherein each pro-ligand comprises at least two donor atoms;
- and
- b. transporting the pro-chelator to an intracellular space of a malignant cell of the subject;
- wherein an active chelator is selectively released from the pro-chelator by reduction of the disulfide bond within the intracellular space,
- wherein the active chelator coordinates Fe selectively within the intracellular space to form a metal complex, and does not coordinate Fe in the bloodstream of the subject, and
- whereby the selective coordination of Fe is effective for treating the malignant cells without causing iron-deficiency anemia.
A pro-chelator according to Formula III, wherein R is H, alkyl, aryl or a derivative thereof.
Dependencies are inferred from the claim text.