Biocompatible flavonoid compounds for organelle and cell imaging

Patent metadata

Field	Value
Publication number	US-10264976-B2
Application number	US-201514934665-A
Country	US
Kind code	B2
Filing date	Nov 6, 2015
Priority date	Dec 26, 2014
Publication date	Apr 23, 2019
Grant date	Apr 23, 2019

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.

First claim

What is claimed is:

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.

Assignees

• Pang Yi
• Liu Bin
• Univ Akron

Inventors

• Pang Yi
• Liu Bin

Classifications

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• C12N2320/35

  based on a specific dosage / administration regimen · CPC title

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title

• C12N2320/30

  Special therapeutic applications · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title