7,8-Dihydroxyflavone

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7,8-Dihydroxyflavone
7,8-dihydroxyflavone.svg
Systematic (IUPAC) name
7,8-Dihydroxy-2-phenyl-4H-chromen-4-one
Identifiers
CAS Number 38183-03-8
ATC code None
PubChem CID: 1880
ChemSpider 1809
Chemical data
Formula C15H10O4
Molecular mass 254.238 g/mol
  • c1ccc(cc1)c2cc(=O)c3ccc(c(c3o2)O)O
  • InChI=1S/C15H10O4/c16-11-7-6-10-12(17)8-13(19-15(10)14(11)18)9-4-2-1-3-5-9/h1-8,16,18H
  • Key:COCYGNDCWFKTMF-UHFFFAOYSA-N

7,8-Dihydroxyflavone (7,8-DHF) is a naturally-occurring flavone found in Godmania aesculifolia, Tridax procumbens, and primula tree leaves.[1][2][3] It has been found to act as a potent and selective small-molecule agonist of the TrkB receptor (Kd ≈ 320 nM), the main signaling receptor of brain-derived neurotrophic factor (BDNF).[4][5][6] 7,8-DHF is both orally-bioavailable and able to penetrate the blood-brain-barrier.[7][8]

7,8-DHF has demonstrated remarkable therapeutic efficacy in animal models of a variety of central nervous system disorders,[6] including depression,[7] Alzheimer's disease,[9][10][11] cognitive deficits in schizophrenia,[12] Parkinson's disease,[4] Huntington's disease,[13] amyotrophic lateral sclerosis,[14] traumatic brain injury,[15] cerebral ischemia,[16][17] fragile X syndrome,[18] and Rett syndrome.[19] 7,8-DHF also shows efficacy in animal models of age-associated cognitive impairment[20] and enhances memory consolidation and emotional learning in healthy rodents.[21][22] In addition, 7,8-DHF possesses powerful antioxidant activity independent of its actions on the TrkB receptor,[23] and protects against glutamate-induced excitotoxicity,[24] 6-hydroxydopamine-induced dopaminergic neurotoxicity,[25] and oxidative stress-induced genotoxicity.[26] It was also found to block methamphetamine-induced dopaminergic neurotoxicity, an effect which, in contrast to the preceding, was found to be TrkB-dependent.[27]

7,8-DHF has been found to act as a weak aromatase inhibitor in vitro (Ki = 10 μM),[28] though there is evidence to suggest that this might not be the case in vivo.[4] In addition, it has been found to inhibit aldehyde dehydrogenase and estrogen sulfotransferase in vitro (Ki = 35 μM and 1–3 μM, respectively), though similarly to the case of aromatase, these activities have not been confirmed in vivo.[4] Unlike many other flavonoids, 7,8-DHF does not show any inhibitory activity on 17β-hydroxysteroid dehydrogenase.[29] 7,8-DHF has also been observed to possess in vitro antiestrogenic effects at very high concentrations (Ki = 50 μM).[30][31]

A variety of close structural analogs of 7,8-DHF have also been found to act as TrkB agonists in vitro, including diosmetin (5,7,3'-trihydroxy-4'-methoxyflavone), norwogonin (5,7,8-trihydroxyflavone), 4'-dimethylamino-7,8-dihydroxyflavone, 7,8,3'-trihydroxyflavone, 7,3'-dihydroxyflavone, 7,8,2'-trihydroxyflavone, 3,7,8,2'-tetrahydroxyflavone, and 3,7-dihydroxyflavone.[32] The highly hydroxylated gossypetin (3,5,7,8,3',4'-hexahydroxyflavone), conversely, appears to be an antagonist of TrkB in vitro.[32]

A prodrug of 7,8-DHF, R7, is under development for the treatment of Alzheimer's disease.[33]

See also

References

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  4. ↑ 4.0 4.1 4.2 4.3 Lua error in package.lua at line 80: module 'strict' not found.
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  6. ↑ 6.0 6.1 Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ 7.0 7.1 Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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  19. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  20. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  21. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  22. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  23. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  24. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  25. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  26. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  27. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  28. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  29. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  30. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  31. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  32. ↑ 32.0 32.1 Lua error in package.lua at line 80: module 'strict' not found.
  33. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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