Materials and Methods Useful to Induce Vacuolization, Cell Death, or a Combination Thereof
AssigneeThe University of Toledo
InventorsWilliam A. Maltese, Paul W. Erhardt, Christopher Trabbic, Jean H. Overmeyer
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Abstract
The present invention provides materials and methods to induce cell death by methuosis, a non-apoptotic cell death mechanism, to induce vacuolization without cell death, or to induce cell death without vacuolization. Small molecules herein are useful for treating cell proliferation disorders or anomalies, particularly, but not exclusively, cancer. Methods related to the research and pharmaceutical use of the small molecules are also provided herein.
Claims28
A compound comprising the structural formula of Formula VIIB:
- wherein:
- O is attached at any one of positions 4, 5, 6, or 7;
- R is alkyl having from 1 to 6 carbon atoms either linear or branched;
- R1 is either:
- alkyl having 2 carbon atoms further substituted at its terminus with a (CO)O-alkyl, (CO)O-aryl, or (CO)O-aralkyl moiety, or
- alkyl having 3 to 6 carbon atoms either linear or branched, aryl, heteroaryl, aralkyl, or heteroaralkyl having from 6 to 12 carbon atoms;
- and
- Ar is aryl or heteroaryl;
- and pharmaceutically acceptable salts, hydrates, and optical isomers thereof.
A compound comprising the structural formula of Formula VIIC:
- wherein:
- O is attached at any of positions 4, 5, 6, or 7;
- R is alkyl having from 1 to 6 carbons either linear or branched;
- R1 is an electron-withdrawing group selected from the group consisting of halide;
- fluorinated alkyl;
- nitro;
- cyano;
- and (CO)R2 or (CO)NHR2, when R2 is selected from the group consisting of alkyl from 1 to 6 linear carbon atoms, aryl, heteroaryl, and aralkyl or heteroalkyl having from 6 to 12 carbon atoms;
- and
- Ar is aryl or heteroaryl;
- and pharmaceutically acceptable salts, hydrates, and optical isomers thereof.
Dependencies are inferred from the claim text.