Dehydroleucodine derivatives and uses thereof

Patent metadata

Field	Value
Publication number	US-11059800-B2
Application number	US-201916283196-A
Country	US
Kind code	B2
Filing date	Feb 22, 2019
Priority date	Jul 11, 2013
Publication date	Jul 13, 2021
Grant date	Jul 13, 2021

Abstract

The present invention provides dehydroleucodine derivatives. In particular, the present invention provides amine derivatives of dehydroleucodine and methods of using dehydroleucodine and the amine derivatives of dehydroleucodine to inhibit the growth of cancer cells.

First claim

What is claimed is:

1. A method for inhibiting growth of a blood cancer cell, wherein the cancer cell is a leukemic cell, the method comprising contacting the cancer cell with an effective amount of composition comprising a compound of Formula (Id), or a pharmaceutically acceptable salt thereof, wherein the composition is effective to inhibit growth of the cancer cell, wherein the compound comprises Formula (Id):

wherein:
R is proline; and
R 3 is selected from hydrogen, CH 3 , CH 2 OH, CH 2 NH 2 , CH 2 Cl, CH 2 Br, CH 2 l or CH 2 F;
R 6 is hydrogen; and
R 8 is selected from hydrogen CH 3 , CH 2 OH, CH 2 NH 2 , CH 2 Cl, CH 2 Br, CH 2 l or CH 2 F.

2. The method of claim 1 , wherein the cancer cell is in vivo or in vitro.

3. The method of claim 1 , wherein the inhibiting growth is measured as the expression of NF-κB.

4. The method of claim 1 , wherein the inhibiting growth is measured as the expression of markers of oxidative stress.

5. The method of claim 4 , wherein the markers of oxidative stress are selected from the group consisting of HMOX1, HSPA1A and HSPH1.

6. The method of claim 1 , wherein the leukemic cell is an acute myeloid leukemia cell, a chronic myeloid leukemia cell, an acute lymphocytic leukemia cell, a chronic lymphocytic leukemia cell, or a cutaneous T cell leukemia.

7. The method of claim 2 , wherein the blood cancer cell is disposed in a subject and the blood cancer cell is contacted by administering the composition comprising a compound of Formula (Id) to the subject.

8. The method of claim 7 , wherein the subject has or is suspected of having acute lymphocytic (lymphoblastic) leukemia, a chronic lymphocytic leukemia, an acute myeloid leukemia, a chronic myeloid leukemia, a hairy cell leukemia, a T-cell prolymphocytic leukemia, a large granular lymphocytic leukemia, or an adult T-cell leukemia.

9. The method of claim 1 , wherein the composition comprising a compound of Formula (Id) selectively inhibits growth of cancer cells and does not appreciably kill non-cancer cells at the same concentration.

Assignees

• Bioventures Llc
• Univ Tecnica Particular De Loja
• Univ Cornell

Inventors

• Compadre Cesar M
• Ordonez Paola E
• Guzman Monica L
• Jones Darin E
• Malagon Omar
• Vidari Giovanni
• Crooks Peter

Classifications

• C07D405/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D307/77

  ortho- or peri-condensed with carbocyclic rings or ring systems · CPC title

• C07D307/93 Primary

  condensed with a ring other than six-membered · CPC title