Anti-cancer compositions and methods

• US 8,003,633 B1
• Filed: 04/14/2009
• Issued: 08/23/2011
• Est. Priority Date: 04/14/2008
• Status: Active Grant

• Current Assignee: Penn State Research Foundation
• Original Assignee: Penn State Research Foundation
• Inventors: Madhunapantula, SubbRao V., Robertson, Gavin P., Desai, Dhimant, Amin, Shantu
• Primary Examiner(s): Padmanabhan; Sreeni
• Assistant Examiner(s): JEAN-LOUIS, SAMIRA JM
• Application Number:
  US12/423,366
• Time in Patent Office: 861 Days
• Field of Search: 514/183
• US Class Current: 514/183
• CPC Class Codes: A61K 31/095 Sulfur, selenium, or tellurium compounds, e.g. thiols
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/33 Heterocyclic compounds
• CPC Class Codes: A61K 8/23 Sulfur; Selenium; Tellurium; Compounds thereof
• CPC Class Codes: C07C 391/00 Compounds containing selenium

Abstract

Anti-cancer compositions and methods are described including one or more compounds having the structural formula I: where R is phenyl, where R1 is (CH₂)_n—Se—C(═NH)—NH₂, where R2 is (CH₂)_n—Se—C(═NH)—NH₂ or R2 is H, and where each n is independently 2, 3, 4, 5, 6, 7, or 8. Methods of treating a subject are provided according to embodiments of the present invention which include administering a therapeutically effective amount of a composition including one or more compounds having the structural formula I to a subject having a condition characterized by Akt dysregulation. Administering a therapeutically effective amount of a composition including one or more compounds having the structural formula I to a subject detectably increases apoptosis and/or decreases proliferation of cancer cells, particularly cancer cells characterized by Akt dysregulation. Compositions of the present invention inhibit Akt enzymes, iNOS, and increase MAP kinase activity such that cancer cells contacted with the compositions are inhibited.

Claims

1. A composition comprising a compound having the structural formula:

R2—

R—

R1, where R is phenyl, where R1 is (CH₂)_n—

Se—

C(═

NH)—

NH₂, where R2 is (CH₂)_n—

Se—

C(═

NH)—

NH₂ or R2 is H, where each n is independently an integer in the range of 2-8, inclusive.

2. The composition of claim 1, wherein the compound has the structural formula:

3. The composition of claim 1 where the compound has the structural formula:

4. The composition of claim 1, wherein the compound has the structural formula:

6. The pharmaceutical composition of claim 5, wherein the compound is The composition of claim 1, wherein the compound has the structural formula selected from the group consisting of:

5. A pharmaceutical composition, comprising:

a compound having the structural formula;

R2—

R—

R1, where R is phenyl, where R1 is (CH₂)_n—

Se—

C(═

NH)—

NH₂, where R2 is (CH₂)_n—

Se—

C(═

NH)—

NH₂ or R2 is H, and where each n is independently an integer in the range of 2-8, inclusive; and

a pharmaceutically acceptable carrier.

7. The composition of claim 5, wherein the pharmaceutical composition is formulated for topical application.