3,3′,4′,5,5′-Pentahydroxyflavone is a potent inhibitor of amyloid β fibril formation

Site-specific Inhibitory Mechanism for Amyloid β42 Aggregation by Catechol-type Flavonoids Targeting the Lys Residues

“…Fisetin, a quercetin analog without the 5-OH group on the A-ring, also inhibited the aggregation of A␤42 (58). Ushikubo et al (59) reported that the 7-OH group on the A-ring is not involved in the anti-aggregative ability of flavonols. These are consistent with our previous study on the structure-activity relationship of (ϩ)-taxifolin (23).…”

A Food and Drug Administration-approved Asthma Therapeutic Agent Impacts Amyloid β in the Brain in a Transgenic Model of Alzheimer Disease

“…Because of its close structural homology with fisetin (3,3Ј,4Ј,7-tetrahydroxyflavone) (27), a neurotrophic molecule that has been shown previously to inhibit amyloid aggregation (28), we hypothesized that cromolyn sodium may potentially prevent A␤ oligomerization and promote A␤ clearance in vitro and in vivo. In addition, the use of cromolyn sodium in addiction models (after subcutaneous infusion (29,30)) and the physical properties of this molecule (molecular weight: 508.38; polar surface area: 125; and LogP: 1.39) argue for cromolyn sodium as a bloodbrain barrier-permeable drug, therefore allowing systemic infusion.…”

“…Because of its structural similarities with fisetin (3,3Ј,4Ј,7-tetrahydroxyflavone, Fig. 1A), a flavonoid compound that has been previously shown to inhibit A␤ polymerization (27,28), we hypothesized that cromolyn sodium may also impact A␤ aggregation processes and modulate A␤ metabolism in vitro and in vivo. To test this hypothesis, we first evaluated the effect of cromolyn sodium on A␤ 40 and A␤ 42 fibrillization using a Thioflavin-T assay.…”

Protein Folding and Aggregation into Amyloid: The Interference by Natural Phenolic Compounds

“…The array of natural phenols being tested as potential inhibitors of amyloid aggregation becomes wider and wider every day and now includes also tannic acid [207,313] and the product of tannin hydrolysis ellagic acid [314]; several flavones, like apigenin [315,316], baicalein [315,317,318], kaempferol [260,261,263,264,271,319], morin [265,320,321], fisetin [259,260,321], rutin (the glycoside of quercetin with the disaccharide rutinose) [322,323] and luteolin [260,324]; rottlerin, already known as a PKC-δ inhibitor [325,326]; the anthocyanidin malvidin, the main responsible for the red color of wine [327]; the stilbenes piceatannol [328] and the resveratrol-derived dimer ɛ-viniferin glucoside [329]; and, finally, ferulic acid (related to trans-cinnamic acid) [189,263,264,330–332]. …”