Methods for preventing and treating cancer using N-thiolated beta-lactam compounds and analogs thereof
AssigneeUniversity of South Florida
InventorsQ. Ping Dou, Edward Turos, David M. Smith
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Abstract
The subject invention concerns N-thiolated β-lactam compounds, their analogs and pharmaceutically acceptable salts, esters and amides thereof. The subject invention also concerns methods for inducing tumor cell death or inhibiting tumor cell proliferation, and methods for inducing DNA damage, inhibiting DNA replication, activating p38 MAP kinase, or activating caspase cascade activation, or releasing cytochrome C from mitochondria into the cytoplasm in a tumor cell. Methods for treating cancer using N-thiolated β-lactam compounds, as well as pharmaceutical compositions comprising the same are further disclosed.
Claims76
An N-thiolated β-lactam compound having the structure of Formula A,
- 8
- in which R1 is a hydrocarbon group having 1-8 carbon atoms;
- R3 is an organothio group;
- and R4 alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, cycloalkenyl, or heterocycloalkenyl, any of which can be optionally substituted with R2, wherein R2 is one or more halides, hydroxyl, nitro, cyano, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, alkoxy, amide, amine, carboxylic ester group, CHO, COOH, or COX, wherein X is Cl, F, Br, or I;
- or a pharmaceutically acceptable salt, ester or amide thereof.
A method for screening a N-thiolated β-lactam compound or an analog thereof for its ability to induce tumor cell death or to inhibit tumor cell proliferation comprising:
- i) contacting a culture of tumor cells with the an effective amount of said N-thiolated β-lactam compound;
- ii) preparing a lysate of the said tumor cells contacted with said N-thiolated β-lactam;
- iii) measuring apoptosis-specific caspase-3 activity or PARP cleavage;
- and
- iv) relating the measured apoptosis specific caspase activity or PARP cleavage to the said N-thiolated β-lactam's or analog thereof's ability to induce tumor cell death or to inhibit tumor cell proliferation.
Dependencies are inferred from the claim text.