Inhibition of fatty acid synthase by beta-lactones and other compounds for inhibition of cellular proliferation

A method of identifying a beta-lactone that inhibits angiogenesis, comprising:

• a) contacting a sample comprising endothelial cells with a beta-lactone having the formula I:
• wherein R1, R2, R3, and R4 are, independently, hydrogen, an alkyl group, a cycloalkyl group, a heterocyloalkyl group, an alkoxy group, a hydroxyalkyl group, a halogenated alkyl group, an alkoxyalkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an aralkyl group, a hydroxy group, an amine group, an amide, an ester, a carbonate group, a carboxylic acid, an aldehyde, a keto group, an ether group, a halide, a urethane group, a silyl group, or a sulfo-oxo group, and wherein the stereochemistry at carbons a and b is R or S;
• and
• b) measuring the amount of endothelial cell proliferation, cell cycle progression, or cell cycle arrest in the sample,
• whereby a decrease in cell proliferation, a decrease in cell cycle progression, or an increase in cell cycle arrest in the sample, relative to the amount of cell proliferation, cell cycle progression, or cell cycle arrest in a sample comprising endothelial cells not contacted with the beta-lactone, identifies a beta-lactone that inhibits angiogenesis.

A method of identifying a beta-lactone that inhibits angiogenesis, comprising:

• a) contacting a sample with a beta-lactone, wherein the sample comprises angiogenic cells and wherein the beta-lactone has the formula I:
• wherein R1, R2, R3, and R4 are, independently, hydrogen, an alkyl group, a cycloalkyl group, a heterocyloalkyl group, an alkoxy group, a hydroxyalkyl group, a halogenated alkyl group, an alkoxyalkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an aralkyl group, a hydroxy group, an amine group, an amide, an ester, a carbonate group, a carboxylic acid, an aldehyde, a keto group, an ether group, a halide, a urethane group, a silyl group, or a sulfo-oxo group, and wherein the stereochemistry at carbons a and b is R or S, and
• b) measuring the amount of angiogenesis in the sample,
• whereby a decrease in the amount of angiogenesis in the sample, relative to the amount of angiogenesis in a sample not contacted with the beta-lactone, identifies a beta-lactone that inhibits angiogenesis.