Contents

Tropoflavin

Chemical compound

Tropoflavin

Clinical data
Other names	7,8-Dihydroxyflavone
Pharmacokinetic data
Bioavailability	~5% (in mice)[1]
Elimination half-life	< 30 minutes (in mice)[1]
Identifiers
IUPAC name 7,8-Dihydroxy-2-phenyl-4H-chromen-4-one
CAS Number	38183-03-8
PubChem CID	1880
ChemSpider	1809
UNII	ADB6MA8ZV2
ChEBI	CHEBI:140464
CompTox Dashboard (EPA)	DTXSID00191568
ECHA InfoCard	100.048.903
Chemical and physical data
Formula	C15H10O4
Molar mass	254.241 g·mol−1
3D model (JSmol)	Interactive image
SMILES c1ccc(cc1)c2cc(=O)c3ccc(c(c3o2)O)O
InChI 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

Tropoflavin, also known as 7,8-dihydroxyflavone, is a naturally occurring flavone found in Godmania aesculifolia, Tridax procumbens, and primula tree leaves.^[2][3][4] It has been found to act as a potent and selective small-molecule agonist of the tropomyosin receptor kinase B (TrkB) (K_d ≈ 320 nM), the main signaling receptor of the neurotrophin brain-derived neurotrophic factor (BDNF).^[5][6][7] Tropoflavin is both orally bioavailable and able to penetrate the blood–brain barrier.^[8][9]Aprodrug of tropoflavin with greatly improved potency and pharmacokinetics, R13 (and, formerly, R7), is under development for the treatment of Alzheimer's disease.^[10][11]

Tropoflavin has demonstrated therapeutic efficacy in animal models of a variety of central nervous system disorders,^[7] including depression,^[8] Alzheimer's disease,^[12][13][14] cognitive deficitsinschizophrenia,^[15] Parkinson's disease,^[5] Huntington's disease,^[16] amyotrophic lateral sclerosis,^[17] traumatic brain injury,^[18] cerebral ischemia,^[19][20] fragile X syndrome,^[21] and Rett syndrome.^[22] Tropoflavin also shows efficacy in animal models of age-associated cognitive impairment^[23] and enhances memory consolidation and emotional learning in healthy rodents.^[24][25] In addition, tropoflavin possesses powerful antioxidant activity independent of its actions on the TrkB receptor,^[26] and protects against glutamate-induced excitotoxicity,^[27] 6-hydroxydopamine-induced dopaminergic neurotoxicity,^[28] and oxidative stress-induced genotoxicity.^[29] It was also found to block methamphetamine-induced dopaminergic neurotoxicity, an effect which, in contrast to the preceding, was found to be TrkB-dependent.^[30]

In 2017, evidence was published suggesting that tropoflavin and various other reported small-molecule TrkB agonists might not actually be direct agonists of the TrkB and might be mediating their observed effects by other means.^[31][32]

Tropoflavin has been found to act as a weak aromatase inhibitor in vitro (K_i = 10 μM),^[33] though there is evidence to suggest that this might not be the case in vivo.^[5] In addition, it has been found to inhibit aldehyde dehydrogenase and estrogen sulfotransferase in vitro (K_i = 35 μM and 1–3 μM, respectively), although similarly to the case of aromatase, these activities have not yet been confirmed in vivo.^[5] Unlike many other flavonoids, tropoflavin does not show any inhibitory activity on 17β-hydroxysteroid dehydrogenase.^[34] Tropoflavin has also been observed to possess in vitro antiestrogenic effects at very high concentrations (K_i = 50 μM).^[35][36]

A variety of close structural analogues of tropoflavin have also been found to act as TrkB agonists in vitro, including diosmetin (5,7,3'-trihydroxy-4'-methoxyflavone), norwogonin (5,7,8-trihydroxyflavone), eutropoflavin (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.^[37] The highly hydroxylated analogue gossypetin (3,5,7,8,3',4'-hexahydroxyflavone), conversely, appears to be an antagonist of TrkB in vitro.^[37]

Tropoflavin was also found to decrease mouse sleep in dark phase and reduce hypothalamus level of orexin A, but not orexin B, in mice.^[38]

See also[edit]

• List of investigational antidepressants
• Tropomyosin receptor kinase B § Agonists

References[edit]