Mito-honokiol compounds and methods of synthesis and use thereof

Patent metadata

Field	Value
Publication number	US-11897910-B2
Application number	US-202017099268-A
Country	US
Kind code	B2
Filing date	Nov 16, 2020
Priority date	Jun 11, 2015
Publication date	Feb 13, 2024
Grant date	Feb 13, 2024

Abstract

The present invention provides mito-honokiol or mito-magnolol compounds, pharmaceutical compositions thereof, and methods of using the mito-honokiol or mito-magnolol compounds in the treatment of cancer.

First claim

We claim:

1. A mito-magnolol compound according to the following structures:

wherein L 1 is

wherein n is an integer from 1-15, and
wherein L 2 is

or H, wherein n is an integer from 1-15.

2. The compound of claim 1 wherein n is an integer from 1-12.

3. The compound of claim 1 , wherein n is 9 or 10.

4. The compound of claim 1 , wherein L 2 is

wherein n is an integer from 1-15.

5. The compound of claim 4 , wherein n is 9 or 10.

6. The compound of claim 1 , wherein L 2 is H.

7. The compound of claim 6 , wherein n of L 1 is an integer from 1-12.

8. The compound of claim 7 , wherein n is 9 or 10.

9. The compound of claim 1 , where the compound is:

10. The compound of claim 1 , wherein the compound is

11. A method of reducing or inhibiting tumor growth in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising at least one mito-magnolol compound of claim 1 , wherein the tumor is melanoma, lung cancer, colon cancer or pancreatic cancer.

12. The method of claim 11 , wherein the tumor is a lung cancer.

13. The method of claim 11 , wherein the tumor is a metastatic tumor.

14. The method of claim 11 , wherein the method further comprises treatment of the patient with an antiglycolytic agent and other standard-of-care drug.

15. The method of claim 11 , wherein the antiglycolytic agent is selected from the group consisting of 2-deoxyglucose or 3-bromopyruvate.

16. The method of claim 11 , wherein the method further comprises treating the patient with surgery, radiation therapy (RT), or chemotherapy (CT) prior to or concurrently with administering the pharmaceutical composition.

17. A method of inhibiting, or reducing metastasis of a cancer comprising administering an effective amount of a pharmaceutical composition comprising at least one mito-magnolol of claim 1 to inhibit or reduce metastasis of cancer in the patient, wherein the cancer is selected from the group consisting of melanoma, colon cancer, lung cancer and pancreatic cancer.

18. The method of claim 17 , wherein the metastasis is in a lymph node or distal organ.

19. The compound of claim 1 , wherein then of both L 1 and L 2 is an integer from 1-12.

Assignees

• Medical College Wisconsin Inc
• Aix Marseille Univ

Inventors

• Kalyanaraman Balaraman
• Zielonka Jacek Michal
• Cheng Gang
• Hardy Micael J
• Ouari Olivier
• You Ming

Classifications

• C07F9/5456 Primary

  Arylalkanephosphonium compounds · CPC title

• A61P35/04 Primary

  specific for metastasis · CPC title

• A61K31/19

  Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60) · CPC title

• A61K31/7004

  Monosaccharides having only carbon, hydrogen and oxygen atoms · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title