β-Secretase (BACE-1) inhibitory effect of biflavonoids

Sasaki, Hiroaki; Miki, Kazuhiko; Kinoshita, Kaoru; Koyama, Kiyotaka; Juliawaty, Lia Dewi; Achmad, Sjamsul A.; Hakim, Euis H.; Kaneda, Miyuki; Takahashi, Kunio

doi:10.1016/j.bmcl.2010.06.021

Cited by 46 publications

(34 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For reasons that are still unclear, other monoflavonoids that are structurally similar to myricetin such as apigenin and morin were found to be less effective at reducing "-secretase activity. On the other hand, a study on "-secretase inhibition has revealed that amentoflavone-type biflavonoids (molar mass 600 Da) potently inhibited "-secretase activity (Sasaki et al 2010). It is believed that biflavoniods, being roughly twice the size of monoflavonoids, better fit the large sized "-secretase catalytic cleft to inhibit "-secretase activity compared to smaller sized monoflavonoids (Ghosh et al 2012).…”

Section: Biflavonoids As Secretase Inhibitorsmentioning

confidence: 98%

Biflavonoids as Potential Small Molecule Therapeutics for Alzheimer’s Disease

Thapa

2015

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Flavonoids are naturally occurring phytochemicals found in a variety of fruits and vegetables and offer color, flavor, aroma, nutritional and health benefits. Flavonoids have been found to play a neuroprotective role by inhibiting and/or modifying the self-assembly of the amyloid-β (Aβ) peptide into oligomers and fibrils, which are linked to the pathogenesis of Alzheimer's disease. The neuroprotective efficacy of flavonoids has been found to strongly depend on their structure and functional groups. Flavonoids may exist in monomeric, as well as di-, tri-, tetra- or polymeric form through C-C or C-O-C linkages. It has been shown that flavonoids containing two or more units, e.g., biflavonoids, exert greater biological activity than their respective monoflavonoids. For instance, biflavonoids have the ability to distinctly alter Aβ aggregation and more effectively reduce the toxicity of Aβ oligomers compared to the monoflavonoid moieties. Although the molecular mechanisms remain to be elucidated, flavonoids have been shown to alter the Aβ aggregation pathway to yield non-toxic, unstructured Aβ aggregates, as well as directly exerting a neuroprotective effect to cells. In this chapter, we review biflavonoid-mediated Aβ aggregation and toxicity, and highlight the beneficial roles biflavonoids can potentially play in the prevention and treatment of Alzheimer's disease.

show abstract

Section: Biflavonoids As Secretase Inhibitorsmentioning

confidence: 98%

Biflavonoids as Potential Small Molecule Therapeutics for Alzheimer’s Disease

Thapa

2015

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

show abstract

“…In continuation to our interest in experimental and theoretical explorations of BACE-1 inhibitors [22,23] and also to further elucidate the binding interactions of biflavonoids with BACE-1 active site, molecular docking simulation and amino acid decomposition analysis [23] of a series of experimentally validated biflavonoids (1-21) [17] were reported here. For more clarification, chemical structures of the selected biflavonoids are summarized in Table 1.…”

Section: Introductionmentioning

confidence: 98%

“…These researchers found out that biflavonoids were better inhibitors of Ab toxicity and fibrillogenesis when compared to monoflavonoids. Table 1 Chemical structures of evaluated biflavonoids [17] Comp. code In another study, Sasaki and colleagues demonstrated that certain biflavonoid structures can be regarded as potent beta-secretase (BACE-1) inhibitors [17].…”

Section: Introductionmentioning

confidence: 99%

“…Table 1 Chemical structures of evaluated biflavonoids [17] Comp. code In another study, Sasaki and colleagues demonstrated that certain biflavonoid structures can be regarded as potent beta-secretase (BACE-1) inhibitors [17]. Some other biflavonoids were successfully isolated from the fruits of Rhus parviflora and showed BACE-1 inhibitory activity [18].…”

Section: Introductionmentioning

confidence: 99%

“…For more clarification, chemical structures of the selected biflavonoids are summarized in Table 1. For the details of preparation methods and measuring BACE-1 inhibitory activities, the original article should be consulted [17].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular docking and quantum mechanical studies on biflavonoid structures as BACE-1 inhibitors

et al. 2014

View full text Add to dashboard Cite

Beta-site amyloid precursor protein cleaving enzyme (BACE-1) is a well-known therapeutic target for Alzheimer disease (AD) due to its characteristic role in the pathogenesis of AD. Numerous researches have been focused on the design and development of potent peptidic and nonpeptidic BACE-1 inhibitors. In the present contribution, a series of experimentally validated biflavonoid BACE-1 inhibitors (1-21) were subjected to our structure-based molecular modeling studies. Binding modes were elucidated through molecular docking in the active site of the enzyme. Relatively good correlations between the theoretical and experimental binding affinities could be achieved (R 2 = 0.61). Analysis of intermolecular binding energy components was performed via functional B3LYP in association with splitvalence basis set using polarization functions (Def2-SVP), and structure-binding relationships were further elucidated through ligand-residue binding energies. Since little studies have been performed on the modeling and structure activity/binding relationships of biflavonoid structures as BACE-1 inhibitors, the results of this study may be useful in further extending the scope of biflavonoid structures as potential anti-Alzheimer scaffolds.

show abstract

Phytomedicine

Malik¹

2017

Neuroprotective Effects of Phytochemicals in Neurological Disorders

View full text Add to dashboard Cite

β-Secretase (BACE-1) inhibitory effect of biflavonoids

Cited by 46 publications

References 19 publications

Biflavonoids as Potential Small Molecule Therapeutics for Alzheimer’s Disease

Biflavonoids as Potential Small Molecule Therapeutics for Alzheimer’s Disease

Molecular docking and quantum mechanical studies on biflavonoid structures as BACE-1 inhibitors

Phytomedicine

Contact Info

Product

Resources

About