Chemical constituents with their alpha-glucosidase inhibitory activity from the whole plant of Ceratophyllum demersum.

From Ceratophyllum demersum growing in Vietnam, twelve compounds were isolated and structurally elucidated, including six previously undescribed compounds, demersones A-D (1-4), acetylvelutins A and B (8 and 9), together with six known compounds, (+)-cyclocolorenone (5), 1-hydroxycyclocolorenone (6), 10-hydroxycyclocolorenone (7), retusin (10), betulinic acid (11), and lupeol (12). The chemical structures and stereochemistry of 1-12 were identified through analysis of spectroscopic data (1D and 2D NMR and HRESIMS), ECD data, and DFT calculation. Notably, this is the first time that humulene-type (1 and 2), guaiane-type (3), and aromadendrane-type (4-7) sesquiterpenoids have been reported in this genus. Compounds 8 and 9 are the first examples of 8-acetoxyflavones found in nature. Upon evaluation of the alpha-glucosidase of 1-3 and 5-12, it was found that 12 exhibited the highest potential with an IC50 value of 15.4 ± 1.1 µM. The molecular docking of 3 and 8 was further studied.

Structural modification of tanshinone IIA and their α-glucosidase inhibitory activity.

α-Glucosidase is one of the therapeutic approaches for treating type 2 diabetes mellitus. Almost 95 % of diabetes patients worldwide have been diagnosed with type 2 diabetes, resulting in 1.5 million fatalities each year. Newly synthesized oxazole-based tanshinone IIA derivatives (1a-n) were designed and evaluated for their inhibitory activity against α-glucosidase enzyme. Eight compounds (1a-d, 1f-g, 1j, and 1m) demonstrated excellent inhibition with IC50 values ranging from 0.73 ± 0.11 to 9.46 ± 0.57 µM as compared to tanshinone IIA (IC50 = 11.39 ± 0.77 µM) and standard acarbose (IC50 = 100.00 ± 0.95 µM). Among this series, 1j bearing two hydroxyls group over the phenyl ring was identified as the most potent α-glucosidase inhibitor with IC50 value of 0.73 ± 0.11 µM. Molecular docking simulations were done for the most active compound to identify important binding modes responsible for inhibition activity of α-glucosidase. In addition, the kinetic study was also performed to understand the mode of inhibition.

Bio-Guided Isolation of Alpha-Glucosidase Inhibitory Compounds from Vietnamese Lichen Roccella Montagnei.

A bio-guided isolation was applied to the Vietnamese lichen Roccella montagnei based on alpha-glucosidase inhibition. Six compounds were isolated and structurally elucidated, including a new ortho depside, montagneside A (1), together with five known compounds, sekikaic acid (2), lanost-7-en-3ß-ol (3), ethyl orsellinate (4), D-montagnetol (5), and D-erythrin (6). Their chemical structures were identified by extensive 1D and 2D NMR analysis, high-resolution mass spectroscopy, and comparisons with those reported in the literature. D-Erythrin (6), a major component, was selected for further modification using Smiles rearrangement. Three erythritol derivatives 6a-6c were synthesized. Compounds 1-3, 6, and 6a-6c were evaluated for alpha-glucosidase inhibition. Compounds 2 and 6a-6c showed significant alpha-glucosidase inhibition with IC50 values ranging from 7.9 to 149 µM, respectively. Molecular docking was applied to the most active compound 6a to clarify the inhibitory mechanism.

Three new constituents from the stems of Knema globularia and their α-glucosidase inhibitory activity.

Three new metabolites (1-3) were isolated from the stems of Knema globularia, along with five known compounds, including kaempferol (4), quercetin (5), isovanillic acid (6), protocatechuic acid (7), and gallic acid (8). Their structures were deduced using NMR spectroscopic, mass spectrometric analyses, and literature data. The absolute configurations of 1-3 were established by electronic circular dichroism (ECD) spectroscopy. α-Glucosidase inhibitory activities of those compounds were evaluated using a spectrophotometric method, compounds 1-3 showed very strong effects towards α-glucosidase with IC50 values 1.59, 0.58 and 1.37 µM, respectively (the positive control, acarbose, IC50 93.63 µM). Simultaneously, enzyme kinetics study indicated that 2 was a mix-type inhibitor. 2 interacted well in the active site of α-glucosidase enzyme, primarily through hydrogen bonds and hydrophobic interactions.

Morusacerane: A new gammacerane triterpenoid from the trunk of Morus Alba linn. with α-glucosidase inhibitory activity.

This phytochemistry investigation on the trunk of Morus alba L. resulted in the isolation of three triterpenoids, including a new gammacerane triterpenoid - morusacerane (1); along with two known compounds of betulinic acid (2) and ursolic acid (3). The structure elucidation was thoroughly conducted based on 1D, 2D-NMR and HRESIMS spectra, followed by a comparison with existing literatures. The evaluation on α-glucosidase inhibitory exhibited the great potential of the application of these isolated compounds in diabetes treatments. The results show that morusacerane (1), betulinic acid (2), and ursolic acid (3) demonstrate the strong inhibitory with the IC50 values of 106.1, 11.12, and 7.20 µM, respectively. All of these compounds interacted well with the allosteric site enzyme α-glucosidase MAL32 through H-bonds and hydrophobic interaction.

Globunoids A-D, undescribed bichalconoid and biflavanoids with α-glucosidase and α-amylase inhibitory activities from Knema globularia stems.

A bichalconoid, globunoid A (1) and three biflavanones, globunoids B-D (2-4), previously undescribed, were isolated from the stems of Knema globularia, along with fourteen known analogues 5-18. The chemical structures of 1-4 were elucidated by the comprehensive spectroscopic analysis including UV, IR, HRESIMS, and NMR; the absolute configurations were determined based on their NOESY data, DP4+ statistical analysis, and ECD calculation. Up to now, compounds 2 and 3 represent the first 3,3″-linked biflavanone structures. Among the isolated compounds, 2, 3, and 2,3-dihydrocalodenin B (6) potently inhibited α-glucosidase and α-amylase activities, with IC50 values in the range 1.1-7.5 µM. Furthermore, the most active compound 6 was found to be a non-competitive inhibitor against these two enzymes.

Identification and α-glucosidase inhibitory activity evaluation of two new coumarins derived from Mansonia gagei J. R. Drumm.

Five coumarins were isolated from the heartwood of Mansonia gagei, which included two newly discovered compounds, namely 11-hydroxypopulene E (1) and mansorin D (2), along with three previously identified compounds. The structures were determined through the utilisation of comprehensive spectroscopic data, ECD calculations, and a thorough comparison with existing literature data. The α-glucosidase inhibitory activities of all isolated compounds were assessed in yeast. Out of the compounds tested, compound 2 exhibited the most significant activity, displaying a percentage inhibition of 34.33% at a concentration of 200 µM.

Antimicrobial sesquiterpenes from the cultured mycobiont Diorygma pruinosum against methicillin-resistant Staphylococcus aureus isolated from Vietnamese street foods.

Traditionally, lichen has been used for many purposes, but there remains a lack of understanding regarding the chemical composition and antimicrobial characteristics of Diorygma pruinosum, a lichen native to Vietnam. In this study, four sesquiterpenes, diorygmones B-E (1-4), one phenolic compound, 3,5-dihydroxy-4-methoxybenzoic acid (5), and one sterol, ß-sitosterol (6), were isolated and structurally elucidated from the cultured mycobiont of the lichen Diorygma pruinosum. Additionally, two compounds, stictic acid (7) and norstictic acid (8), were also isolated from the lichen D. pruinosum. Compounds 2-4 were new compounds. Their chemical structures were established using comprehensive spectroscopic data, and the absolute configurations were confirmed through the analysis of NOESY and electronic circular dichroism (ECD). Moreover, Staphylococcus aureus, a Gram-positive bacterium, has been responsible for various infections, including food poisoning. Herein, we identified and isolated 13 strains of S. aureus from street food sources. Among these strains, one was identified as a multidrug-resistant variant, designated as SAX15, and was subsequently used for further antimicrobial testing. Compounds 1-3 produced zones of inhibition against S. aureus SAX15 (each 5 mm) in comparison to commercial drugs such as penicillin, ciprofloxacin, gentamicin, cefoxitin, and clarithromycin, which displayed inhibitory zones of 7, 5, 10, 9.7, and 7 mm, respectively.

Bio-guided isolation of alpha-glucosidase inhibitory compounds from Vietnamese Garcinia schomburgkiana fruits: in vitro and in silico studies.

Garcinia schomburgkiana is an edible tree widely distributed in the southern region of Vietnam. Little is known about the alpha-glucosidase inhibition of the Vietnamese Garcinia schomburgkiana. The aim of the current study was to explore the anti-diabetic potential of G. schomburgkiana fruits. All the fractions of G. schomburgkiana were evaluated for alpha-glucosidase inhibition, followed by bioassay-guided isolation. A new compound, epi-guttiferone Q (1), together with ten known compounds, guttiferones I-K (2-3), hypersampsone I (4), sampsonione D (5), sampsonione H (6), ß-mangostin (7), α-mangostin (8), 9-hydroxycalabaxanthone (9), and fuscaxanthone (10), were isolated and structurally elucidated. The structure of the new metabolite 1 was confirmed through 1D and 2D NMR spectroscopy, and MS analysis. To the best of our knowledge, the metabolites (except 3) have not been isolated from this plant previously. All isolated compounds were evaluated for their alpha-glucosidase inhibition. Compounds 1-6 showed potent activity with IC50 values ranging from 16.2 to 130.6 µM. Compound 2 was further selected for a kinetic study. The result indicated that it was a competitive type. Additionally, in silico docking was employed to predict the binding mechanism of 1-2 and 4-6 in the active site of alpha-glucosidase, suggesting their potential as promising anti-diabetic compounds. Molecular dynamic simulation was also applied to 1 to better understand its inhibitory mechanism.

Parmoferone A, a new depsidone from the lichen Parmotrema cristiferum.

A new depsidone, parmoferone A (1), together with three known compounds, parmosidone K (2), albifolione (3), and 4-chloroorcinol (4) were isolated from the lichen Parmotrema cristiferum (Taylor) Hale (Parmeliaceae). The structures of isolated compounds were identified from its spectroscopic data and by comparison with the literature. Compounds 1-4 were evaluated for alpha-glucosidase inhibition. Compound 1 was determined to be a potent non-competitive inhibitor against alpha-glucosidase with an IC50 value of 18.1 µM.

A new neolignan and a new phenolic acid from the heartwood of Mansonia gagei J.R. Drumm.

One new neolignan (1) and one new phenolic compound (2), together with four known compounds (3-6) were isolated from the heartwood of Mansonia gagei. Their structures were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR and HRESIMS. The absolute configuration of 2 was established based on the DP4+ protocol and by comparison of experimental and calculated ECD spectra. All isolated compounds were evaluated by DPPH assay for antioxidant activity, while compounds 3-6 were assayed using the MTT-based colorimetric assay for cytotoxicity against lung cancer cell line A549. In terms of antioxidant activity, 1 and 3 exhibited stronger activity (IC50 14.91 ± 1.10 and 17.46 ± 0.16 µM, respectively) than the positive control, ascorbic acid (IC50 30.20 ± 0.47 µM). Among the compounds tested for cytotoxicity, compound 3 showed the highest activity, with an IC50 value of 26.04 ± 2.95 µM.

α-Glucosidase Inhibitors from the Stems of Knema globularia.

Six new compounds, globunones A-F (1-6), and two new flavonoids (7 and 8) together with nine known compounds (9-17) were isolated from the stems of Knema globularia. The chemical structures of 1-8 were elucidated by an analysis of their NMR and high-resolution electrospray ionization mass spectrometry data as well as by comparison with literature values. The absolute configurations were determined using time-dependent density functional theory electronic circular dichroism (TD-DFT-ECD). Globunones A-E (1-5) represent the initial combined structures of a flavan-3-ol core and a 1,4-benzoquinone core. Globunone F (6) is the first flavanone-type compound bearing a 2-(2,4-dihydroxyphenyl)-2-oxoethyl group found to date in Nature. Compounds 1-3 and 6-17 were tested for their yeast α-glucosidase inhibitory activity. All compounds tested (except for 13 and 14) showed potent inhibition toward α-glucosidase with IC50 values in the range 0.4-26.6 µM. Calodenin A (15) was the most active compound with an IC50 value of 0.4 µM (the positive control, acarbose, IC50 93.6 µM). A kinetic analysis of 15 revealed that it is a noncompetitive inhibitor with a Ki value of 3.4 µM.

Norquandrangularic acid D, a new trinorcycloartane isolated from the leaves of Combretum quadrangulare.

Phytochemical investigation on the leaves of Combretum quadrangulare growing in Vietnam afforded a new trinorcycloartane triterpenoid, norquandrangularic acid D (1), along with three known compounds, betulinic acid (2), luteolin (3), and apigenin (4). Their structures were elucidated using spectroscopic methods and comparison was made with reports in the literature. Compounds 1 and 3 were evaluated for α-glucosidase inhibition. Compound 3 showed significant activity, with an IC50 value of 11.39 µM, (acarbose, used as a positive control, had an IC50 of 367 µM).