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.

Bioactive-Guided Phytochemical Investigations, In Vitro and In Silico Alpha-Glucosidase Inhibition of Two Vietnamese Medicinal Plants Dicranopteris linearis and Psychotria adenophylla.

Little is known about the chemical and biological profiles of Dicranopteris linearis and Psychotria adenophylla. No previous studies have investigated alpha-glucosidase inhibition using extracts from D. linearis and P. adenophylla. In this paper, bioactive-guided isolation procedures were applied to the plants D. linearis and P. adenophylla based on alpha-glucosidase inhibition. From the most active fractions, 20 compounds (DL1-DL13 and PA1-PA7) were isolated. The chemical structures were elucidated using spectroscopic data and compared with those available in the literature. These compounds were evaluated for alpha-glucosidase inhibition, while a molecular docking study was performed to elucidate the mechanisms involved. Consequently, D. linearis and P. adenophylla might serve as a good potential for developing new antidiabetic preparations.

A New Carvotacetone Derivative from the Aerial Part of Sphaeranthus africanus.

Sphaeranthus africanus L. is native in Vietnam. Little is known about α-glucosidase inhibition of Sphaeranthus africanus and its isolated compounds. A bioactive-guided isolation was applied to the Vietnamese Sphaeranthus africanus to find α-glucosidase inhibitory components. Eight compounds were detected and structurally elucidated. They are 3-angeloyloxy-5-[2'',3''-epoxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[3''-chloro-2''-hydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2''R,3''R-dihydroxy-2''-methyl-butanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2''S,3''R-dihydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2''S,3''S-dihydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 5-angeloyloxy-7-hydroxy-3-tigloyloxycarvotacetone, 3-O-methylquercetin, and chrysosplenol D. Their chemical structures were elucidated by extensive 1D and 2D NMR analysis and high-resolution mass spectroscopy as well as comparisons in literature. 3-Angeloyloxy-5-[2''S,3''S-dihydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone is a new compound. Isolated compounds were evaluated for the α-glucosidase inhibition. Isolated compounds showed moderate activity with IC50 values ranging from 128.9-274.3 µM while others are weak. A molecular docking study was conducted, indicating that isolated compounds are potent α-glucosidase inhibitory compounds.

Tecomastane, a new megastigmane from the flowers of Tecoma stans.

Tecoma stans is a tropical plant that is widely used in folk medicine. Little is known about the chemical constituents of flowers of this plant. From flowers of the native plant in Vietnam, 12 compounds were isolated and elucidated, including one new compound tecomastane (1) and eleven known compounds, (3S,5R,6S,7E)-5,6-epoxy-3-hydroxy-7-megastigmane-9-one (2), bosciallin (3), chakyunglupulin B (4), (2S,6R)-2,6-dimethyloctane-1,8-diol (5), cleroindicin F (6), rengyoxide (7), 3,4-dihydroxybenzoic acid (8), methyl 3,4-dihydrobenzoate (9), 3,5-dihydroxybenzoic acid (10), luteolin (11), and indole-3-carboxylic acid (12). Compound 5 was a new natural product. The chemical structures of isolated compounds were identified by interpretation of their spectroscopic data (1D, 2D NMR, and HRESIMS) and by comparison with the literature. Compounds 1-7 and 10-12 were evaluated for alpha-glucosidase inhibition and antimicrobial activity against antibiotic-resistant, pathogenic bacteria Enterococcus faecium, Staphylococcus aureus, and Acinetobacter baumannii.

Two new phenolic compounds from Boerhavia erecta collected in Vietnam.

Boerhavia erecta is a tropical plant that is widely used in Asian folk medicine. Little is known about the alpha-glucosidase inhibition and antimicrobial properties of compounds from this plant. In the present study, the phytochemical study of the aerial parts of B. erecta collected in Vietnam was conducted using multiple chromatographic methods. The chemical structures of isolated compounds were identified by comprehensive spectroscopic methods. Two new compounds, berectone C (1) and (E)-tetracosyl 3-(3-hydroxy-4-methoxyphenyl)acrylate (4), together with the known compounds boeravinone C (2), liquiritigenin (3), bis(1H-indol-3-yl)methanone (5), and indole-3-carboxylic acid (6) were isolated and structural elucidated. Compounds 1 and 4 were evaluated for alpha-glucosidase inhibition and antimicrobial activity against antibiotic-resistant, pathogenic bacteria Enterococcus faecium, Staphylococcus aureus, and Acinetobacter baumannii. Compound 1 showed strong inhibition of the alpha-glucosidase enzyme (IC50 43 µg/mL). Only compound 1 exhibited antimicrobial property against A. baumannii, forming an inhibition zone of 11 mm.

Alpha-glucosidase inhibitors from Nervilia concolor, Tecoma stans, and Bouea macrophylla.

Tecoma stans (L.) Juss. Ex Kunth is widely used in folk medicine. In ethnomedicine, it is applied as a cardioprotective, hepatoprotective, antiarthritic, antinociceptive, anti-inflammatory, and antimicrobial. The aqueous extract is considered antidiabetic, and is used as a traditional remedy in Mexico. More than 120 chemical constituents have been identified in its leaves, barks, and roots. However, less is known about the phytochemical properties of T. stans flower extracts. The herbal plant Nervilia concolor (Blume) Schltr. is native to Vietnam, and is used in traditional Chinese medicine to treat diseases such as bronchitis, stomatitis, acute pneumonia, and laryngitis. Only two previous reports have addressed the chemical content of this plant. Bouea macrophylla Griff., commonly known as marian plum or plum mango, is a tropical plant that is used to treat a range of illnesses. Phytochemical analysis of B. macrophylla suggests the presence of volatile components and flavonoids. However, existing data have been obtained from screening without isolation. As part of our ongoing search for alpha-glucosidase inhibitors from Vietnamese medicinal plants, we conducted bioactive-guided isolation of the whole plant N. concolor, the flowers of T. stans, and the leaves of B. macrophylla. We isolated and structurally elucidated five known compounds from T. stans: ursolic acid (TS1), 3-oxours-12-en-28-oic acid (TS2), chrysoeriol (TS3), ferulic acid (TS4), and tecomine (TS5). Three known compounds were isolated from Nervilia concolor: astragalin (NC1), isoquercitrin (NC2), and caffeic acid (NC3). From B. macrophylla, betullinic acid (BM1), methyl gallate (BM2), and 3-O-galloyl gallic acid methyl ester (BM3) were isolated. All compounds showed promising alpha-glucosidase inhibition, with IC50 values ranging from 1.4 to 143.3 µM. The kinetics of enzyme inhibition showed BM3 to be a competitive-type inhibitor. An in silico molecular docking model confirmed that compounds NC1, NC2, and BM3 were potential inhibitors of the α-glucosidase enzyme. Molecular dynamics simulations were carried out with compound BM3 demonstrating the best docking model during simulation up to 100 ns to explore the stability of the complex ligand-protein.

A new diterpenoid from the leaves of Phyllanthus acidus.

A new diterpenoid, phyllane C (1), along with three known compounds, ovoideal E (2), spruceanol (3), and fluacinoid B (4) were isolated from the leaves of Phyllanthus acidus growing in Thailand. The structures were determined by analysis of their MS and NMR data as well as by comparison with literature values. DFT-NMR chemical shift calculations and subsequent DP4/DP4+ probability methods were applied to define the relative configuration of 1. Compound 3 showed a weak cytotoxicity against K562 cell line (IC50 41.9 ± 2.31 µg/mL).

A new depsidone from the lichen Usnea ceratina Arch.

Chemical investigation of the lichen Usnea ceratina Arch led to the isolation of five depsidones, including one new compound ceratinalone (1) along with four known compounds bailesidone (2), stictic acid (3), 8'-O-methylstictic acid (4) and 8'-O-ethylstictic acid (5). The structures were determined by analysis of their MS and NMR data as well as by comparison with literature values. Compounds 1 and 4 were evaluated the cytotoxic activity against HeLa (human epithelial carcinoma), NCI-H460 (human lung cancer), HepG2 (liver hepatocellular carcinoma), and MCF-7 (human breast cancer) cell lines, showing the moderate activity.

Ricicomin A, a new alkaloid from the leaves of Ricinus communis Linn.

From the leaves of Ricinus communis Linn., one new alkaloid, named ricicomin A (1) together with three known ones, ricinine (2), N-demethylricinine (3) and 4-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid (4) were justified by repeated chromatographic methods. Their structures were determined by comprehensive IR, HR-ESI-MS and NMR analyses. Compound 4 was identified for the first time from the genus Ricinus. DFT-NMR chemical shift calculations and subsequent DP4+ probability methods were applied to confirm the chemical structure of 1. Compounds 1-3 did not display cytotoxic effect against three human cancer cell lines (MCF-7, HepG2 and HeLa) using SRB assay.

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).

Identification of Highly Potent α-Glucosidase Inhibitors from Artocarpus integer and Molecular Docking Studies.

A new natural Diels-Alder adduct (3) was isolated from the leaves and stem bark of Artocarpus integer, along with seventeen known compounds (1, 2, and 4-18). Structural elucidation was conducted using NMR and HR-ESI-MS data, and comparisons were made with previous studies. Deoxyartonin I (3) exhibited the most potent α-glucosidase inhibition (IC50 7.80±0.1 µM), outperforming the acarbose positive control. This was mixed-mode inhibition, as indicated by the intersect in the second quadrant of each respective plot. An in silico molecular docking model and the pharmacokinetic features of 3 suggest that it is a potential inhibitor of enzyme α-glucosidase, and is therefore a lead candidate as a drug against diabetes mellitus.

Flavones from Combretum quadrangulare Growing in Vietnam and Their Alpha-Glucosidase Inhibitory Activity.

Combretum quadrangulare Kurz is widely used in folk medicine in Eastern Asia and is associated with various ethnopharmacological properties including hepatoprotective, antipyretic, analgesic, antidysenteric, and anthelmintic activities. Previous phytochemical investigations reported the presence of numerous triterpenes (mostly cycloartanes, ursanes, lupanes, and oleananes) along with dozens of flavonoids. However, the extracts of C. quadrangulare and isolated flavonoids have not been evaluated for their alpha-glucosidase inhibition. In the frame of our efforts dedicated to the chemical investigation of Vietnamese medicinal plants and their biological activities, a phytochemical study of the MeOH extract of the leaves of C. quadrangulare using bioactive guided isolation was undertaken. In this paper, the isolation and structure elucidation of twelve known compounds, 5-hydroxy-3,7,4'-trimethoxyflavone (1), ayanin (2), kumatakenin (3), rhamnocitrin (4), ombuin (5), myricetin-3,7,3',5'-tetramethyl ether (6), gardenin D (7), luteolin (12), apigenin (13), mearnsetin (14), isoorientin (15), and vitexin (16) were reported. Bromination was applied to compounds 2 and 3 to provide four new synthetic analogues 8-11. All isolated and synthesized compounds were evaluated for alpha-glucosidase inhibition and antibacterial activity. Compounds 4 and 5 showed moderate antibacterial activity against methicillin-resistant Staphylococcus aureus while others were inactive. All compounds failed to reveal any activity toward extended spectrum beta-lactamase-producing Escherichia coli. Compounds 2, 4, 6-9, and 11-14 showed good alpha-glucosidase inhibition with IC50 values in the range of 30.5-282.0 µM. The kinetic of enzyme inhibition showed that 8 and 11 were noncompetitive type inhibition against alpha-glucosidase. In silico molecular docking model indicated that compounds 8 and 11 were potential inhibitors against enzyme α-glucosidase.

Phytochemical Screening and Evaluation of Antioxidant Properties and Antimicrobial Activity against Xanthomonas axonopodis of Euphorbia tirucalli Extracts in Binh Thuan Province, Vietnam.

Euphorbia tirucalli is a medicine plant possessing many bioactive properties. This paper focused on phytochemical screening (alkaloid, flavonoid, saponin, tannin, and anthraquinone), quantification of polyphenol and flavonoids, and activating evaluation of antioxidants and antimicrobial properties against Xanthomonas axonopodis of different extracts from Euphorbia tirucalli grown in Binh Thuan, Vietnam. The best activity fraction was used for purification and determining bioactive ingredients. The results showed that the phytochemical study revealed the presence of alkaloids, flavonoids, tannins, and terpenoids in the ethyl acetate fraction. Saponin and anthraquinone did not present in all extracts. The content of polyphenol and flavonoid of Euphorbia tirucalli stem was in the range of 16.65-106.32 mg EqAG/g and 97.97-450.83 µg QE/g. The ethyl acetate fraction showed higher amounts of polyphenol and flavonoids and antimicrobial activity against X. axonopodis than other fractions. The antioxidant (SC50) activity of Euphorbia tirucalli stem was in the range of 12.91 ± 0.70 and 528.33 ± 25.15 µg/mL. At concentrations of 5.0 and 7.5 mg/mL, the diameter of inhibition of the ethyl acetate fraction was 14.33 ± 0.76 mm and 17.87 ± 0.57 mm, respectively. The MIC (minimum inhibitory concentration) was 0.156 mg/mL. Scopoletin, gallic acid, and piperic acid got MICs corresponding to 78, 312, and 312 µg/mL, respectively. Scopoletin, gallic acid, and piperic acid were found in the ethyl acetate fraction of Euphorbia tirucalli and exhibited the treatment of citrus bacteria canker and plant diseases.

29-Norlupane-1ß-hydroxy-3,20-dione, a new norlupane triterpenoid from the twigs and leaves of Phyllanthus acidus.

A new norlupane triterpenoid, 29-norlupane-1ß-hydroxy-3,20-dione (1), along with ten known compounds, 29-norlup-1-ene-3,20-dione (2), phyllanthol (3), phyllanthone (4), glochidone (5), lupeol (6), lupeone (7), 4-hydroxybenzoic acid (8), 4-hydroxybenzaldehyde (9), phyllane A (10) and methyl ß-orsellinate (11) were isolated the twigs and leaves of Phyllanthus acidus. The structure of 1 was identified by interpretation of their spectroscopic data and comparison with those reported in the literature. In addition, all isolated compounds 1-11 were evaluated for their antioxidant activity.

Manilkzapotane, a novel dimeric alkylresorcinol derivative from the stem bark of Manilkara zapota.

A novel dimeric alkylresorcinol derivative, manilkzapotane (1), along with seven known compounds, lupeol acetate (2), lupeol (3), arjunolic acid (4), ergosterol peroxide (5), taraxerol (6), hederagonic acid (7), and glochidiol (8) were isolated from the stem bark of Manilkara zapota. Their structures were determined on the basis of spectroscopic data. DFT-NMR chemical shift calculations and a modified probability (DP4+) method were applied to define the relative configuration of 1. To the best of our knowledge, this represents the first isolation of a dimeric alkylresorcinol derivative from the Sapotaceae family.

A thorough evaluation of matrix-free laser desorption ionization on structurally diverse alkaloids and their direct detection in plant extracts.

Alkaloids represent a major group of natural products (NPs), derived from highly diverse organisms. These structurally varied specialized metabolites are widely used for medicinal purposes and also known as toxic contaminants in agriculture and dietary supplements. While the detection of alkaloids is generally facilitated by GC- or LC-MS, these techniques do require considerable efforts in sample preparation and method optimization. Bypassing these limitations and also reducing experimental time, matrix-free laser desorption ionization (LDI) and related methods may provide an interesting alternative. As many alkaloids show close structural similarities to matrices used in matrix-assisted laser desorption ionization (MALDI), they should ionize upon simple laser irradiation without matrix support. With this in mind, the current work presents a systematic evaluation of LDI properties of a wide range of structurally diverse alkaloids. Facilitating a direct comparison between LDI and ESI-MS fragmentation, all tested compounds were further studied by electrospray ionization (ESI). Moreover, crude plant extracts of Atropa belladonna, Cinchona succirubra, and Colchicum autumnale were analyzed by LDI in order to evaluate direct alkaloid detection and dereplication from complex mixtures. Finally, dose-dependent evaluation of MALDI and LDI detection using an extract of Rosmarinus officinalis spiked with atropine, colchicine, or quinine was conducted. Overall, present results suggest that LDI provides a versatile analytical tool for analyzing structurally diverse alkaloids as single compounds and from complex mixtures. It may further serve various potential applications ranging from quality control to the screening for toxic compounds as well as the build up of MS databases. Graphical abstract.

Salazinic Acid-Derived Depsidones and Diphenylethers with α-Glucosidase Inhibitory Activity from the Lichen Parmotrema dilatatum.

Three new depsidones, parmosidones F - G (1 - 2), and 8'-O-methylsalazinic acid (3), and 3 new diphenylethers, parmetherines A - C (4 - 6), together with 2 known congeners were isolated from the whole thalli of Parmotrema dilatatum, a foliose chlorolichen. Their structures were unambiguously determined by extensive spectroscopic analyses and comparison with literature data. The isolated polyphenolics were assayed for their α-glucosidase inhibitory activities. Newly reported benzylated depsidones 1: and 2: in particular inhibited α-glucosidase with IC50 values of 2.2 and 4.3 µM, respectively, and are thus more potent than the positive control, acarbose.

Anticancer Activity of Novel Plant Extracts and Compounds from Adenosma bracteosum (Bonati) in Human Lung and Liver Cancer Cells.

Cancer is the second leading cause of death globally, and despite the advances in drug development, it is still necessary to develop new plant-derived medicines. Compared with using conventional chemical drugs to decrease the side effects induced by chemotherapy, natural herbal medicines have many advantages. The present study aimed to discover the potential cytotoxicity of ethanol extract and its derived fractions (chloroform, ethyl acetate, butanol, and aqueous) of Adenosma bracteosum Bonati. (A. bracteosum) on human large cell lung carcinoma (NCI-H460) and hepatocellular carcinoma (HepG2). Among these fractions, the chloroform showed significant activity in the inhibition of proliferation of both cancerous cells because of the presence of bioactive compounds including xanthomicrol, 5,4'-dihydroxy-6,7,8,3'-tetramethoxyflavone, and ursolic acid which were clearly revealed by nuclear magnetic resonance spectroscopy (1H-NMR, 13C-NMR, Heteronuclear Multiple Bond Coherence, and Heteronuclear Single Quantum Coherence Spectroscopy) analyses. According to the radical scavenging capacity, the 5,4'-dihydroxy-6,7,8,3'-tetramethoxyflavone compound (AB2) exhibited the highest anticancer activity on both NCI-H460 and HepG2 with IC50 values of 4.57 ± 0.32 and 5.67 ± 0.09 µg/mL respectively, followed by the ursolic acid with the lower percent inhibition at 13.05 ± 0.55 and 10.00 ± 0.16 µg/mL, respectively (p < 0.05). Remarkably, the AB2 compound induced to significant increase in the production of reactive oxygen species accompanied by attenuation of mitochondrial membrane potential, thus inducing the activation of caspase-3 activity in both human lung and liver cancer cells. These results suggest that A. bracteosum is a promising source of useful natural products and AB2 offers opportunities to develop the novel anticancer drugs.

α-Glucosidase Inhibitory Depsidones from the Lichen Parmotrema tsavoense.

Chemical investigation of the lichen Parmotrema tsavoense led to the isolation of 5 new depsidones, parmosidones F - J (1:  - 5: ). These compounds were structurally elucidated using spectroscopic methods including HRESIMS and 2D NMR data. Compounds 1, 3: , and 4: were evaluated for their inhibition of α-glucosidase. All exhibited potent α-glucosidase inhibitory activity with IC50 values ranging from 10.7 to 17.6 µM, which was much lower than that of the positive control acarbose (IC50 449 µM).