Curcumin conjugates and methods of use thereof

Patent metadata

Field	Value
Publication number	US-10660967-B2
Application number	US-201715790498-A
Country	US
Kind code	B2
Filing date	Oct 23, 2017
Priority date	Oct 21, 2016
Publication date	May 26, 2020
Grant date	May 26, 2020

Abstract

Curcumin-based conjugates and methods of use thereof are provided. Pharmaceutical compositions including an effective amount of one or more curcumin conjugates are also provided. In particular embodiments, the compositions are formulated for oral delivery. The conjugates and pharmaceutical compositions thereof can be administered to a subject in need thereof to treat a host of diseases and disorders including but not limited to, cancer, inflammation, and microbial growth.

First claim

What is claimed is:

1. A curcumin conjugate of the general formula

wherein the dotted lines between A and C 1 , C 1 and C 2 , C 2 and C 3 and C 3 and D indicate that a single or double bond may be present, as valence permits,
wherein the dotted lines between A and M, and D and Q indicate that a single bond or no bond may be present, as valence permit,
wherein C 1 , C 2 , and C 3 are carbon atoms,
wherein A and D are oxygen atoms,
wherein M and Q are independently absent, or hydrogen, as valence permits,
wherein R 2 and R 3 can be one or more amino acids or salts thereof, nucleic acids, lipids, polysaccharides, polymers, substituted or unsubstituted alkyl groups, alkenyl groups, alkynyl groups, aryl groups, heteroaryl groups, or other organic groups containing between C 1 and C 10 carbon atoms, inclusive,
wherein R 1 and R 4 can be carboxybenzyl (Cbz), or fluorenylmethyloxycarbonyl (FMOC), and
wherein L 1 and L 2 can be independently absent, substituted or unsubstituted alkyl groups, alkenyl groups, alkynyl groups, aryl groups, heteroaryl groups, or other organic groups containing between C 1 and C 10 carbon atoms, inclusive or a combination thereof or pharmaceutically acceptable salt(s), polymorph(s), solvent(s), hydrate(s), crystal forms, and/or enantiomer(s) thereof.

2. The curcumin conjugate of claim 1 , wherein M and Q are absent, the bond between A and C 1 , and D and C 3 are double bonds, and the bonds between C 1 and C 2 , and C 2 and C 3 are single bonds.

3. The curcumin conjugate of claim 1 , wherein (i) the bond between C 1 and A is a double bond, M is absent, the bond between C 1 and C 2 is a single bond, the bond between C 2 and C 3 is a double bond, the bond between C 3 and D is a single bond, and Q is hydrogen, or (ii) the bond between C 3 and D is a double bond, Q is absent, the bond between C 2 and C 3 is a single bond, the bond between C 1 and C 2 is a double bond, the bond between C 1 and A is a single bond, and M is hydrogen.

4. The curcumin conjugate of claim 1 , wherein R 2 and R 3 are each independently an amino acid and R 1 and R 4 are each independently carboxybenzyl (Cbz) or fluorenylmethyloxycarbonyl (FMOC).

5. The curcumin conjugate of claim 1 , wherein the conjugate consists of the structure of any one of the following compounds:

6. A pharmaceutical composition comprising an effective amount of at least one of the curcumin conjugates of claim 1 .

7. The pharmaceutical composition of claim 6 , further comprising a pharmaceutically acceptable excipient.

8. The pharmaceutical composition of claim 6 , wherein the composition is formulated for oral delivery.

9. A pharmaceutical composition comprising a curcumin conjugate selected from the group consisting of ((1E,6E)-3,5-dioxohepta-1,6-diene-1,7-diyl)bis(2-methoxy-4,1-phenylene) bis(2-(((benzyloxy)carbonyl)amino)propanoate), ((1E,6E)-3,5-dioxohepta-1,6-diene-1,7-diyl)bis(2-methoxy-4,1-phenylene) (2S,2′S)-bis(2-(((benzyloxy)carbonyl)amino)-4-(methylthio)butanoate), ((1E,6E)-3,5-dioxohepta-1,6-diene-1,7-diyl)bis(2-methoxy-4,1-phenylene) bis(2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)acetate), ((1E,6E)-3,5-dioxohepta-1,6-diene-1,7-diyl)bis(2-methoxy-4,1-phenylene) (2S,2'S)-bis(2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(methylthio)butanoate), ((1E,6E)-3,5-dioxohepta-1,6-diene-1,7-diyl)bis(2-methoxy-4,1-phenylene) (2R,2′R)-bis(2-(((benzyloxy)carbonyl)amino)propanoate), and ((1E,6E)-3,5-dioxohepta-1,6-diene-1,7-diyl)bis(2-methoxy-4,1-phenylene) (2R,2′R)-bis(2-(((benzyloxy)carbonyl)amino)-4-(methylthio)butanoate), or a combination thereof or pharmaceutically acceptable salt(s), polymorph(s), solvent(s), hydrate(s), crystal forms, and/or enantiomer(s) thereof.

10. The pharmaceutical composition of claim 6 , wherein the composition is optically pure.

11. A method of treating cancer in a subject in need thereof comprising administering the subject an effective amount of the pharmaceutical composition of claim 6 , wherein the cancer is breast cancer, colon cancer, liver cancer, lung cancer, or prostate cancer.

12. A method of treating an infection in a subject in need thereof comprising administering the subject an effective amount of the pharmaceutical composition of claim 6 , wherein the infection is caused by a microbe selected from the group consisting of Staphylococcus aureus, Streptococcus pyogenes, Salmonella Typhi, Pseudomonas aeruginosa , and Candida albicans.

Assignees

• Univ Res Inst Inc Augusta

Inventors

• Panda Siva

Classifications

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• C07C271/22

  to carbon atoms of hydrocarbon radicals substituted by carboxyl groups · CPC title

• C07C69/96

  Esters of carbonic or haloformic acids · CPC title

• C07C237/06

  having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms · CPC title

• C07C233/51

  having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings · CPC title