Compositions and methods for attenuating mitochondria-mediated cell injury

• US 20060122267A1
• Filed: 12/20/2005
• Published: 06/08/2006
• Est. Priority Date: 11/25/2003
• Status: Abandoned Application

• Current Assignee: University of Rochester
• Original Assignee: University of Rochester
• Inventors: Anders, Marion W., Sheu, Shey-Shing, Brookes, Paul S.
• Application Number:
  US11/316,618
• Publication Number:
  US 20060122267A1
• Time in Patent Office: Days
• US Class Current: 514/509
• CPC Class Codes: A61K 31/21 Esters, e.g. nitroglycerine, selenocyanates
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 5/0215 containing natural amino acids, forming a peptide bond via their side chain functional group, e.g. epsilon-Lys, gamma-Glu

Abstract

The present invention relates to a S-nitrosated mitochondria-targeted thiol-based antioxidant prodrug and uses therefore for the prevention or treatment of diseases or conditions associated with mitochondrial dysfunction resulting from changes in the mitochondrial redox environment. When activated, prodrug of the present invention can specifically provide a NO^• donor and a thiol-based antioxidant to mitochondria thereby decreasing the degree of mitochondrial dysfunction.

Claims

1. A S-nitrosated mitochondria-targeted thiol antioxidant prodrug.

2. A pharmaceutical composition comprising the prodrug of claim 1 in admixture with a pharmaceutically acceptable carrier.

3. A method for delivering nitric oxide to mitochondria of a cell comprising contacting a cell or tissue with a mitochondria-targeted thiol antioxidant prodrug of claim 1, thereby delivering nitric oxide to the mitochondria of the cell or cells of the tissue.

4. A method for decreasing the degree of mitochondrial dysfunction resulting from changes in the mitochondrial redox environment comprising contacting a cell or tissue with an effective amount of a mitochondria-targeted thiol antioxidant prodrug of claim 1, thereby decreasing the degree of mitochondrial dysfunction in the cell resulting from changes in the mitochondrial redox environment.

5. A method for preventing or treating a disease or condition associated with mitochondrial dysfunction resulting from changes in the mitochondrial redox environment comprising administering to a subject an effective amount of a pharmaceutical composition of claim 2 so that a disease or condition associated with mitochondrial dysfunction in the subject is prevented or treated.