IP Library Granted Patent US 10,264,976
Granted Patent B2
US 10,264,976 · App. 14/934,665 · Granted Apr 23, 2019

Biocompatible flavonoid compounds for organelle and cell imaging

Inventors: Yi Pang (Copley, OH); Bin Liu (Akron, OH)
Assignee: The University of Akron
A61B5/0071A61K49/0021C07D311/30C07F9/6533C12N15/113C12N15/1135C12N15/1137C12Q1/02G01N33/582H05K999/99A61K31/713C12N2310/14C12N2310/322C12N2310/344C12N2310/3515C12N2310/531C12N2320/30C12N2320/32C12N2320/35C12N2320/53
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Quick Facts
Patent No.
US 10,264,976
App. No.
14/934,665
Granted
Apr 23, 2019
Kind
B2
Abstract

Flavonoid compounds may be prepared that are selective for certain cell organelles, and may be used as biological imaging agents. Organelles that may be imaged with flavonoid compounds include mitochondria and lysosomes. Advantageously, the flavonoids show specificity to certain organelles and may exhibit a florescence “turn-on” mechanism, where the flavonoids that have target an organelle exhibit a florescence response when excited.

Claims (28)

1. A flavonoid compound defined by the formula

where each R 1 -R 4 is individually an organic group or an hydrogen atom, R 5 and R 6 are each individually an organic group or an hydrogen atom or where R 5 and R 6 combine to form a single organic group, each R 7 is individually an organic group, and n is about 3 to 10 units.

2. The flavonoid of claim 1 , where the flavonoid compound is defined by the formula

where each R 10 -R 4 is individually an organic group or an hydrogen atom, each R 7 is individually an organic group, and n is about 3 to 10 units.

3. The flavonoid of claim 1 , where the flavonoid compound is defined by the formula

where n is about 3 to 10 units.

4. The flavonoid of claim 1 , where the flavonoid compound is defined by the formula

where R 5 and R 6 are earch individually an organic group or an hydrogen atom or where R 5 and R 6 combine to form a single organic group and n is about 3 to 10 units.

5. A flavonoid compound defined by the formula

where each R 1 , R 3 , and R 4 is individually an organic group or an hydrogen atom, R 5 and R 6 are each individually an organic group or an hydrogen atom or where R 5 and R 6 combine to form a single organic group, R 8 is an organic group or a hydrogen atom, R 9 is an organic group or a hydrogen atom, R 11 and R 12 are each individually an organic group or an hydrogen atom or where R 11 and R 12 combine to form a single organic group, and n is about 1 to 6 units.

6. A method of imaging an organelle comprising

combining a mitochondrion and a flavonoid compound and allowing the flavonoid compound to stain the mitochondrion, where the flavonoid compound is defined by the formula

 where each R 1 -R 4 is individually an organic group or an hydrogen atom, R 5 and R 6 are each individually an organic group or an hydrogen atom or where R 5 and R 6 combine to form a single organic group, each R 7 is individually an organic group, and n is about 3 to 10 units;

irradiating the stained mitochondrion with an excitation wavelength that excites the flavonoid compound and induces a fluorescence response; and

capturing an image of the fluorescence response.

7. The method of claim 6 , where the mitochondrion is an isolated cell-free mitochondrion.

8. The method of claim 6 , where the mitochondrion is present in a eukaryotic cell.

9. The method of claim 8 , where the eukaryotic cell is a stem cell.

10. The method of claim 6 , where the step of allowing the flavonoid compound to stain the mitochondrion is performed by incubating a mitochondrion with about 0.02 μM to about 10 μM of the flavonoid compound at about 37° C. for about 25 min in a growth medium.

11. A method of imaging an organelle comprising

combining a lysosome of a eukaryotic cell and a flavonoid compound and allowing the flavonoid compound to stain the lysosome, where the flavonoid compound is defined by the formula

 where each R 1 , R 3 , and R 4 is individually an organic group or a hydrogen atom, R 5 and R 6 are each individually an organic group or a hydrogen atom or where R 5 and R 6 combine to form a single organic group, R 8 is an organic group or a hydrogen atom, R 9 is an organic group or a hydrogen atom, R 11 and R 12 are each individually an organic group or a hydrogen atom or where R 11 and R 12 combine to form a single organic group, and n is about 1 to 6 units;

irradiating the stained lysosome with an excitation wavelength that excites the flavonoid compound and induces a fluorescence response; and

capturing an image of the fluorescence response.

12. The method of claim 11 , where the lysosome is an isolated cell-free lysosome.

13. The method of claim 11 , where the lysosome is in a eukaryotic cell.

14. The method of claim 13 , where the eukaryotic cell is a stem cell.

15. The method of claim 11 , where the step of allowing the flavonoid compound to stain the lysosome is performed by incubating a lysosome with about 0.02 μM to about 10 μM of the flavonoid compound at about 37° C. for about 25 min in a growth medium.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 10, 2018
From: PANG, YI; LIU, BIN
To: THE UNIVERSITY OF AKRON
Reel/Frame 047115/0780 →
CONFIRMATORY LICENSE Recorded Aug 4, 2016
From: UNIVERSITY OF AKRON
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 039562/0218 →
Continuity (2)
Provisional Application 62184290 · Jun 25, 2015
Related Publication 20160376296A1 · Dec 29, 2016