Agigenin

Revisiting the South Indian Traditional Plants against Several Targets of SARS-CoV-2 - An in silico Approach.[Pubmed:36588334]

Curr Comput Aided Drug Des. 2023;19(3):202-233.

BACKGROUND: The south Indian Telugu states will celebrate a new year called 'Ugadi' which is a south Indian traditional festival. The ingredients used in ugadi pachadi have often also been used in food as well as traditional Ayurveda and Siddha medicinal preparations. Coronaviruses (CoVs) are a diverse family of enveloped positive-sense single-stranded RNA viruses which can infect humans and have the potential to cause large-scale outbreaks. OBJECTIVE: Considering the benefits of ugadi pachadi, we investigated the binding modes of various phytochemical constituents reported from its ingredients against five targets of SARS-CoV-2. METHODS: Flexible-ligand docking simulations were achieved through AutoDock version 1.5.6. Following 50ns of molecular dynamics simulation using GROMACS 2018.1 software and binding free energy (DeltaG(bind)) of the protein-ligand complexes were calculated using the g_mmpbsa tool. ADME prediction was done using Qikprop of Schrodinger. RESULTS: From the molecular docking and MM/PBSA results compound Eriodictin exhibited the highest binding energy when complexed with nucleocapsid N protein (6M3M) (-6.8 kcal/mol, - 82.46 kJ/mol), bound SARS-CoV-2-hACE2 complex (6M0J) (-7.4 kcal/mol, -71.10 kJ/mol) and Mpro (6XR3) (-8.6 kcal/mol, -140.21 kJ/mol). Van der Waal and electrostatic energy terms highly favored total free energy binding. CONCLUSION: The compounds Eriodictin, Vitexin, Cycloart-3, 24, 27-triol, Agigenin, Mangiferin, Mangiferolic acid, Schaftoside, 27-Hydroxymangiferonic acid, Quercetin, Azadirachtol, Cubebin, Isomangiferin, Isoquercitrin, Malicarpin, Orientin and procyanidin dimer exhibited satisfactory binding energy values when compared with standard molecules. The further iterative optimization of high-ranked compounds following validation by in vitro and in vivo techniques assists in discovering therapeutic anti-SARS-CoV-2 molecules.

Spirostanol Saponins from Flowers of Allium Porrum and Related Compounds Indicating Cytotoxic Activity and Affecting Nitric Oxide Production Inhibitory Effect in Peritoneal Macrophages.[Pubmed:34770942]

Molecules. 2021 Oct 29;26(21):6533.

Saponins, a diverse group of natural compounds, offer an interesting pool of derivatives with biomedical application. In this study, three structurally related spirostanol saponins were isolated and identified from the leek flowers of Allium porrum L. (garden leek). Two of them were identical with the already known leek plant constituents: aginoside (1) and 6-deoxyaginoside (2). The third one was identified as new component of A. porrum; however, it was found identical with yayoisaponin A (3) obtained earlier from a mutant of elephant garlic Allium ampeloprasun L. It is a derivative of the aginoside (1) with additional glucose in its glycosidic chain, identified by MS and NMR analysis as (2alpha, 3beta, 6beta, 25R)-2,6-dihydroxyspirostan-3-yl beta-D-glucopyranosyl-(1 --> 3)-beta-D-glucopranosyl-(1 --> 2)-[beta-D-xylopyranosyl-(1 --> 3)]-beta-D-glucopyranosyl]-(1 --> 4)-beta-D-galactopyranoside, previously reported also under the name alliporin. The leek native saponins were tested together with other known and structurally related saponins (tomatonin and digitonin) and with their related aglycones (Agigenin and diosgenin) for in vitro cytotoxicity and for effects on NO production in mouse peritoneal cells. The highest inhibitory effects were exhibited by 6-deoxyaginoside. The obtained toxicity data, however, closely correlated with the suppression of NO production. Therefore, an unambiguous linking of obtained bioactivities of saponins with their expected immunobiological properties remained uncertain.

Antifungal saponins from bulbs of garlic, Allium sativum L. var. Voghiera.[Pubmed:22513009]

Phytochemistry. 2012 Jun;78:126-34.

A bioassay-guided phytochemical analysis of the polar extract from the bulbs of garlic, Allium sativum L., var. Voghiera, typical of Voghiera, Ferrara (Italy), allowed the isolation of ten furostanol saponins; voghieroside A1/A2 and voghieroside B1/B2, based on the rare agapanthagenin aglycone; voghieroside C1/C2, based on Agigenin aglycone; and voghieroside D1/D2 and E1/E2, based on gitogenin aglycone. In addition, we found two known spirostanol saponins, Agigenin 3-O-trisaccharide and gitogenin 3-O-tetrasaccharide. The chemical structures of the isolated compounds were established through a combination of extensive nuclear magnetic resonance, mass spectrometry and chemical analyses. High concentrations of two eugenol diglycosides were also found for the first time in Allium spp. The isolated compounds were evaluated for their antimicrobial activity towards two fungal species, the air-borne pathogen Botrytis cinerea and the antagonistic fungus Trichoderma harzianum.

Anti-HBV active flavone glucosides from Euphorbia humifusa Willd.[Pubmed:20450964]

Fitoterapia. 2010 Oct;81(7):799-802.

Thirteen flavone glucosides from the herb of Euphorbia humifusa were isolated and elucidated. Among them, five compounds including apigenin-7-O-beta-D-glucopyranoside (2), apigenin-7-O-(6''-O-galloyl)-beta-D-glucopyranoside (3), luteolin-7-O-beta-D-glucopyranoside (7), luteolin-7-O-(6''-O-trans-feruloyl)-beta-D-glucopyranoside (8) and luteolin-7-O-(6''-O-coumaroyl)-beta-D-glucopyranoside (9) showed anti-HBV activity in vitro. The structure-activity relationship showed that the parent structure was closely relevant to the anti-HBV activity of these compounds (Agigenin>luteolin>quercetin). It was found that the number of glucoside in the structure may significantly influence their activities (flavone monoglucoside>flavone diglucoside) and cytotoxicity (flavone>flavone monoglucoside>flavone diglucoside). In addition, the substitution of acyl group on glucoside may be important to keep the anti-HBV activities of these compounds (galloyl>feruloyl>coumaroyl).

Porrigenins A and B, novel cytotoxic and antiproliferative sapogenins isolated from Allium porrum.[Pubmed:9358643]

J Nat Prod. 1997 Oct;60(10):1003-7.

Four new sapogenins, porrigenins A (2a) and B (3a), identified as (25R)-5 alpha-spirostan-2 beta,3 beta,6 beta-triol and (25R)-2-oxo-5 alpha-spirostan-3 beta,6 beta-diol, respectively, and neoporrigenins A (2b) and B (3b) were also isolated from Allium porrum. In addition, the known Agigenin (1a) and its 25S epimer, neoAgigenin (1b), were also identified. Their structure elucidation was provided by comprehensive spectroscopic analyses. Compounds 1a, 2a, and 3a exhibited cytotoxicity and high antiproliferative activity on four different tumor cell lines in vitro.

[Experimental study of the anabolic activity of 6-ketoderivatives of certain natural sapogenins].[Pubmed:1028596]

Farmakol Toksikol. 1976 Sep-Oct;39(5):631-5.

It is shown that 6-ketoderivatives of natural sapogenins, viz. Agigenin, diosgenin and alliogenin, display the anabolic activity and do not manifest any androgenic properties. The compoud IV/(25 R)-5alpha-spirostan-2alpha, 3beta, 5alpha-triol-6-OH/produces an accelerated gain of weight in rats, and also an increase in the weight of the liver, heart, kidneys, musculus tibiliasis anterior and augments the total amount of protein therein. All of the above-mentioned changes become more pronounced with the study substance introduced to young animals. Castration of sexually immature rats greatly mitigates the anabolic effect of the compound IV.