Curcumin analogues as zinc chelators and their uses
AssigneesThe Research Foundation for The State University of New York, Chem-Master International, Inc.
InventorsFrancis Johnson, Lorne Golub
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Abstract
This invention provides a compound having the structure wherein α, β, X, Y, and R1-R11 are defined herein. This invention also provides a pharmaceutical composition comprising the above compounds, a method of inhibiting the activity and/or levels of a matrix metalloproteinase (MMP), a method of inhibiting the production of a cytokine in a population of cells, a method of inhibiting the production of a growth factor in a population of cells, and a method of inhibiting NFκ-B activation in a population of cells.
Claims20
A method of increasing water solubility, metal binding ability, MMP inhibition activity, cytokine inhibition activity, growth factor inhibition activity, or NFKB activation inhibition activity of curcumin comprising synthesizing a compound having the structure
- wherein
- bond α and β are each, independently, present or absent;
- X is CR5 or N;
- Y is CR10 or N;
- R1 is H or an electron-withdrawing group;
- R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are each independently, H, halogen, —NO2, —CN, —NR28R29, —NHR28R29+, —SR28, —SO2R28, —OR28, —CO2R28, CF3, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, heteroaryl, or heterocyclyl;
- wherein R28 and R29 are each, H, CF3, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, or —C(=0) -heterocyclyl;
- and
- wherein when R1 is H, R3, R4, R5, R8, R9, or R10, is halogen, —NO2, —CN, —NR28R29, —NHR28R29+, —SR28, —SO2R28, —CO2R28, CF3, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, heteroaryl, or heterocyclyl;
- wherein R28 and R29 are each, H, CF3, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, or —C(=0) -heterocyclyl;
- and
- wherein each occurrence of alkyl, alkenyl, or alkynyl is branched or unbranched, unsubstituted or substituted;
- or a salt thereof.
A method of inhibiting the production of a cytokine in a population of mammalian cells comprising contacting the population of cells with a compound having the structure
- wherein
- bond α and β are each, independently, present or absent;
- X is CR5 or N;
- Y is CR10 or N;
- R1 is H or an electron-withdrawing group;
- R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are each independently, H, halogen, —NO2, —CN, —NR28R29, —NHR28R29+, —SR28, —SO2R28, —OR28, —CO2R28, CF3, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, heteroaryl, or heterocyclyl;
- wherein R28 and R29 are each, H, CF3, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, or —C(=0)-heterocyclyl;
- and
- wherein when R1 is H, R3, R4, R5, R8, R9, or R10, is halogen, —NO2, —CN, —NR28R29, —NHR28R29+, —SR28, —SO2R28, —CO2R28, CF3, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, heteroaryl, or heterocyclyl;
- wherein R28 and R29 are each, H, CF3, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, or —C(=0) -heterocyclyl;
- and
- wherein each occurrence of alkyl, alkenyl, or alkynyl is branched or unbranched, unsubstituted or substituted;
- or a salt thereof;
- so as to inhibit the production of a cytokine, wherein the population of cells is a population of human cells.
A method of inhibiting the production of a growth factor in a population of mammalian cells comprising contacting the population of cells with a compound having the structure
- wherein
- bond α and β are each, independently, present or absent;
- X is CR5 or N;
- Y is CR10 or N;
- R1 is H or an electron-withdrawing group;
- R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are each independently, H, halogen, —NO2, —CN, —NR28R29, —NHR28R29+, —SR28, —SO2R28, —OR28, —CO2R28, CF3, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, heteroaryl, or heterocyclyl;
- wherein R28 and R29 are each, H, CF3, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, or —C(=0) -heterocyclyl;
- and
- wherein when R1 is H, R3, R4, R5, R8, R9, or R10, is halogen, —NO2, —CN, —NR28R29, —NHR28R29+, —SR28, —SO2R28, —CO2R28, CF3, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, heteroaryl, or heterocyclyl;
- wherein R28 and R29 are each, H, CF3, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, or —C(=0)-heterocyclyl;
- and
- wherein each occurrence of alkyl, alkenyl, or alkynyl is branched or unbranched, unsubstituted or substituted;
- or a salt thereof;
- so as to inhibit production of a growth factor, wherein the growth factor is VEGF, PDGF, TGF-β, or MIP1α.
Dependencies are inferred from the claim text.