2,3-Dihydroamentoflavone

Exploration of natural compounds with anti-SARS-CoV-2 activity via inhibition of SARS-CoV-2 Mpro.[Pubmed:33406222]

Brief Bioinform. 2021 Mar 22;22(2):1361-1377.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a dreaded pandemic in lack of specific therapeutic agent. SARS-CoV-2 Mpro, an essential factor in viral pathogenesis, is recognized as a prospective therapeutic target in drug discovery against SARS-CoV-2. To tackle this pandemic, Food and Drug Administration-approved drugs are being screened against SARS-CoV-2 Mpro via in silico and in vitro methods to detect the best conceivable drug candidates. However, identification of natural compounds with anti-SARS-CoV-2 Mpro potential have been recommended as rapid and effective alternative for anti-SARS-CoV-2 therapeutic development. Thereof, a total of 653 natural compounds were identified against SARS-CoV-2 Mpro from NP-lib database at MTi-OpenScreen webserver using virtual screening approach. Subsequently, top four potential compounds, i.e. 2,3-Dihydroamentoflavone (ZINC000043552589), Podocarpusflavon-B (ZINC000003594862), Rutin (ZINC000003947429) and Quercimeritrin 6"-O-L-arabinopyranoside (ZINC000070691536), and co-crystallized N3 inhibitor as reference ligand were considered for stringent molecular docking after geometry optimization by DFT method. Each compound exhibited substantial docking energy >-12 kcal/mol and molecular contacts with essential residues, including catalytic dyad (His41 and Cys145) and substrate binding residues, in the active pocket of SARS-CoV-2 Mpro against N3 inhibitor. The screened compounds were further scrutinized via absorption, distribution, metabolism, and excretion - toxicity (ADMET), quantum chemical calculations, combinatorial molecular simulations and hybrid QM/MM approaches. Convincingly, collected results support the potent compounds for druglikeness and strong binding affinity with the catalytic pocket of SARS-CoV-2 Mpro. Hence, selected compounds are advocated as potential inhibitors of SARS-CoV-2 Mpro and can be utilized in drug development against SARS-CoV-2 infection.

[Flavonoids from Selaginella uncinata].[Pubmed:26677701]

Zhongguo Zhong Yao Za Zhi. 2015 Aug;40(15):3005-8.

In the current study, nine flavonoids were isolated and purified from 75% ethanol extract of Selaginella uncinata (Desv.) Spring by column chromatographic techniques over macroporous resin, polyamide, silica gel, Sephadex LH-20 and pre-HPLC. On the basis of their physico-chemical properties and spectroscopic data analyses, these compounds were elucidated as cirsimarin (1), nepitrin (2), apigenin-6-C-alpha-L-arabinopyranosyl-8-C-beta-D-glucopyranoside (3), apigenin-6-C-beta-D-glucopyranosyl-8-C-alpha-L-arabinopyranoside (4), apigenin-7-O-beta-D-glucopyranoside (5), 2,3-Dihydroamentoflavone (6), 4'-O-methylamentoflavone (7), 2,3-dihydro-4'-O-methyl-amentoflavone (8), and 2,3,2",3"-tetrahydron-4'-O-methyl-robustaflavone (9). Compounds 1-5 belong to flavonoid glycosides and were isolated from the genus Selaginella for the first time.

Anti-diabetic molecules from Cycas pectinata Griff. traditionally used by the Maiba-Maibi.[Pubmed:25636866]

Phytomedicine. 2015 Jan 15;22(1):23-6.

Bioactivity guided chemical investigation on active anti-diabetic constituents of the fruits of Cycas pectinata Griff. (FCP) characterized EAFr-5 as the most potent sub fraction which significantly reduced the blood glucose level to normal in STZ induced diabetic rats. It was shown to contain the biflavonoids amentoflavone (1) and 2,3-Dihydroamentoflavone (2) which exhibited significantly high inhibitory potency against alpha-glucosidase (IC50 8.09 +/- 0.023 and 9.77 +/- 0.032 muM, respectively) and alpha-amylase (IC50 73.6 +/- 0.48 and 39.69 +/- 0.39 muM, respectively). This is the first report of bioactivity guided isolation of anti-diabetic constituents from the traditionally used fruits of Cycas pectinata Griff.

Bioguided fractionation and isolation of natural inhibitors of advanced glycation end-products (AGEs) from Calophyllum flavoramulum.[Pubmed:22445651]

Phytochemistry. 2012 Jun;78:98-106.

Advanced glycation end-products (AGEs) are associated with many pathogenic disorders such as Alzheimer's disease, pathogenesis of diabetes, atherosclerosis or endothelial dysfunction leading to cardiovascular events. Clusiaceae and Calophyllaceae families are rich in compounds like polyphenols which are able to inhibit their formation and are therefore of great interest. Calophyllum flavoramulum Hend. & Wyatt-Sm., a native Malaysian plant, was selected after an anti-AGEs screening conducted on DCM and MeOH extracts from plants belonging to these aforementioned families. In a first study, bioguided fractionation of the MeOH leaf extract of C. flavoramulum afforded amentoflavone, 3-methoxy-2-hydroxyxanthone, 3,4-dihydroxy-tetrahydrofuran-3-carboxylic acid, quercitrin, 3,4-dihydroxybenzoic acid, canophyllol and apetalactone. Amentoflavone and 3-methoxy-2-hydroxyxanthone were found to be very potent (IC(50)=0.05 and 0.06 mM respectively), while anti-AGEs activities of quercitrin and 3,4-dihydroxybenzoic acid appeared as moderately strong (IC(50)=0.5 mM). In a second study, a systematic phytochemical study of the cyclohexane, DCM and EtOAc extracts obtained from the same plant was conducted to isolate the following products: flavoramulone, 6-deoxyjacareubin, rheediachromenoxanthone, 2,3-Dihydroamentoflavone and benzoic acid. 3,4-Dihydroxy-tetrahydrofuran-3-carboxylic acid and flavoramulone were isolated for the first time and their structures were identified by means of IR, MS and NMR spectrometries.

beta-Secretase (BACE-1) inhibitory effect of biflavonoids.[Pubmed:20598535]

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4558-60.

Here, we describe amentoflavone-type biflavonoids, which were isolated from natural sources and were found to inhibit beta-secretase (BACE-1). The structure-activity relationship was studied, and compounds 1-8, 10, 17, and 18 showed BACE-1 inhibitory activity. Among these compounds, 2,3-Dihydroamentoflavone 17 and 2,3-dihydro-6-methylginkgetin 18 exhibited potent inhibitory effects with IC(50) values of 0.75 and 0.35 microM, respectively.

A new glucoside from Selaginella sinensis.[Pubmed:16931428]

J Asian Nat Prod Res. 2006 Sep;8(6):529-33.

A new glucoside, selaginoside (1), together with two known compounds, hinokiflavone (2) and 2,3-Dihydroamentoflavone (3), were isolated from the whole plants of Selaginella sinensis. Their structures were elucidated by means of spectroscopic methods.

New cytotoxic biflavonoids from Selaginella delicatula.[Pubmed:16041653]

Planta Med. 2005 Jul;71(7):659-65.

Five new biflavonoids, robustaflavone 7,4',4'''-trimethyl ether, robustaflavone 4',4'''-dimethyl ether, 2,3-Dihydroamentoflavone 7,4',7''-trimethyl ether, 2,3-Dihydroamentoflavone 7,4'-dimethyl ether, and 2'',3''-dihydroisocryptomerin 7-methyl ether, together with six known compounds have been isolated from the aerial parts of Selaginella delicatula. The structures of these new compounds were determined through spectral analyses. Among the isolates, robustaflavone 4',4'''-dimethyl ether, 2,3-Dihydroamentoflavone 7,4'-dimethyl ether, and alpha-tocopheryl quinone exhibited cytotoxicities (ED50 values < 4 microg/mL) against P-388 and/or HT-29 cell lines in vitro.

Sterols, triterpenes and biflavonoids of Viburnum jucundum and cytotoxic activity of ursolic acid.[Pubmed:11582553]

Planta Med. 2001 Oct;67(7):683-4.

The triterpenes ursolic acid (1), 27-p-Z-coumaroyloxyursolic acid (2), 27-p-E-coumaroyloxyursolic acid, alpha-amyrine-3-palmitate and lupeol-3-palmitate were isolated through a bioactivity-guided fractionation from the acetonic extract of the aerial parts of Viburnum jucundum Morton in addition to amentoflavone, an epimeric mixture at C-2 of 2,3-Dihydroamentoflavone, beta-sitosterol and beta-sitosteryl glucopyranoside. Ursolic acid (1) was the only constituent that exhibited cytotoxic activity toward three human cancer cell lines in culture. This is the first phytochemical and cytotoxic analysis performed to this plant species.