Glabrolide

In silico Inhibition of BACE-1 by Selective Phytochemicals as Novel Potential Inhibitors: Molecular Docking and DFT Studies.[Pubmed:30767744]

Curr Drug Discov Technol. 2019 Feb 14. pii: CDDT-EPUB-96664.

BACKGROUND: Alzheimer's disease (AD) has become the most common age-dependent disease of dementia. The trademark pathologies of AD are the presence of amyloid aggregates in neurofibrils. Recently phytochemicals being considered as potential inhibitors against various neurodegenerative, anti-fungal, antibacterial and antiviral diseases in human beings. OBJECTIVE: This study targets the inhibition of BACE-1 by phytochemicals using in silico drug discovery analysis. METHODS: A total of 3150 phytochemicals were collected from almost 25 different plants through literature assessment. The ADMET studies, molecular docking and density functional theory (DFT) based analysis was performed to analyze the potential inhibitory properties of these phytochemicals. RESULTS: The ADMET and docking results exposed seven compounds that have high potential as an inhibitory agent against BACE-1 and show binding affinity >8.0 kcal/mol against BACE-1. They show binding affinity greater than those of various previously reported inhibitors of BACE-1. Furthermore, DFT based analysis shown high reactivity for these seven phytochemicals in the binding pocket of BACE-1, based on ELUMO, EHOMO and Kohn-Sham energy gap. Seven out of seven phytochemicals are testified (as compared to experimental ones) as novel inhibitors against BACE-1. CONCLUSION: Out of seven phytochemicals, four are from plant Glycyrrhiza glabra i.e. Shinflavanone, Glabrolide, Glabrol and PrenyllicoflavoneA, one from Huperzia serrate i.e. Macleanine, one from Uncaria rhynchophylla i.e. 3a-dihydro-cadambine and another one is VolvalerelactoneB from plant Valeriana-officinalis. It is concluded that these phytochemicals are candidate for drug/inhibitor against BACE-1, and can be administered to humans after experimental validation through in vitro and in vivo trials.

Saponin and sapogenol. XLVIII. On the constituents of the roots of Glycyrrhiza uralensis Fischer from northeastern China. (2). Licorice-saponins D3, E2, F3, G2, H2, J2, and K2.[Pubmed:8403082]

Chem Pharm Bull (Tokyo). 1993 Aug;41(8):1337-45.

Following the characterization of licorice-saponins A3 (2), B2 (3), and C2 (4), the chemical structures of licorice-saponins D3 (5), E2 (6), F3 (7), G2 (8), H2 (9), J2 (10), and K2 (11), seven of the ten oleanane-type triterpene oligoglycosides isolated from the air-dried roots of Glycyrrhiza uralensis Fischer collected in the northeastern part of China, were investigated. On the basis of chemical and physicochemical evidence, the structures of licorice-saponins D3, E2, F3, G2, H2, J2, and K2 have been determined to be expressed as 3 beta-[alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucuronopyranosyl(1-- >2)-beta-D-glucuronopyranosyloxy]-22 beta-acetoxyolean-12-en-30-oic acid (5), 3-O-[beta-D-glucuronopyranosyl(1-->2)-beta-D- glucuronopyranosyl]Glabrolide (6), 3-O-[alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucuronopyranosyl(1--> 2)-beta-D-glucuronopyranosyl]-11-deoxoGlabrolide (7), 24-hydroxyglycyrrhizin (8), 3-O-[beta-D-glucuronopyranosyl(1-->2)-beta- D-glucuronopyranosyl]liquiritic acid (9), 24-hydroxy-11-deoxoglycyrrhizin (10), and 3 beta-[beta-D- glucuronopyranosyl(1-->2)-beta-D-glucuronopyranosyloxy]-24-+ ++hydroxyoleana- 11,13(18)-dien-30-oic acid (11), respectively.