A new diphenyl ether from the cultured lichen mycobiont of Graphis cf. handelii.

Lichen is well-known for its various purposes. However, understanding the chemical composition and antimicrobial characteristics of Graphis cf. handelii remains insufficient. In this study, a new compound, graphinone A (1), together with three known compounds, handelone (2), 4-O-methylhiascic acid (3), and ethyl orsellinate (4) were isolated and structurally elucidated. Their chemical structures were established using comprehensive spectroscopic data (1D- and 2D-NMR and HRESIMS). Compounds 1-4 were tested for antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) and evaluated for the alpha-glucosidase inhibition.

Diphenyl ethers from the cultured lichen mycobiont of Graphis handelii Zahlbr.

Purpose: Cultured lichen mycobionts are valuable sources of new natural compounds. Mycobiont of Graphis handelii growing in Vietnam was isolated, cultivated and chemically investigated. The crude extract of this cultured mycobiont showed potent alpha-glucosidase inhibition with an IC50 value of 50 µg/mL. Methods: Multiple chromatographic methods were applied to the extract to isolate compounds. The combination of Nuclear Magnetic Resonance analysis and high-resolution mass spectroscopy determined their chemical structures. Electrophilic bromination/chlorination was applied to obtain new derivatives using NaBr/H2O2 and NaCl/H2O2 reagents. Compounds were evaluated for enzyme inhibitory activities, including alpha-glucosidase inhibition, HIV-1 reverse transcriptase inhibition, SARS-CoV-2 main protease (Mpro) inhibition, anti-inflammatory activity, and cytotoxicity against several cancer cell lines. A molecular docking study for anti-SARS-CoV-2 was conducted to understand the inhibitory mechanism. Results: A new diphenyl ether, handelone (1) and a known compound xylarinic acid A (2) were isolated and elucidated. Four synthetic products 6'-bromohandelone (1a), 2'-bromohandelone (1b), 2',6'-dibromohandelone (1c), and 2',6'-dichlorohandelone (1d) were prepared. Compound 1 showed good activity against Mpro with an IC50 value of 5.2 µM but it showed weak or inactive activity in other tests. Other compounds were inactive in all assays. Conclusion: A new compound, handelone (1) was isolated from the cultured mycobiont of Graphis handelii. From these compounds, four new derivatives were prepared. Compound 1 showed good activity against Mpro with an IC50 value of 5.2 µM but it showed weak or inactive activity in other tests. Other compounds were inactive in all assays.

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.

New Halogenated Flavonoids from Adenosma bracteosum and Vitex negundo and Their α-Glucosidase Inhibition.

Adenosma bracteosum and Vitex negundo are natural sources of methoxylated flavonoids. Little is known about the α-glucosidase inhibition of multi-methoxylated flavonoid derivatives. Eighteen natural flavonoids were isolated from A. bracteosum and V. negundo. Seven halogenated derivatives were synthesized. Their chemical structures were elucidated by extensive NMR analysis and high-resolution mass spectroscopy as well as comparisons in literature. All compounds were evaluated for their α-glucosidase inhibition. Most compounds showed good activity with IC50 values ranging from 16.7 to 421.8 µM. 6,8-Dibromocatechin was the most active compound with an IC50 value of 16.7 µM. A molecular docking study was conducted, indicating that those compounds are potent α-glucosidase inhibitors.

Indicuen, a new hopane from Parmotrema indicum Hale growing in Vietnam.

One new hopane-type triterpene, indicuen (1), along with eight known compounds (2-9) were isolated from the n-hexane extract of the lichen Parmotrema indicum Hale. The chemical structures of isolated compounds were identified by interpretation of their spectroscopic data (1D, 2D NMR and HRESIMS) combined with DFT-NMR chemical shift calculations and subsequent assignment of DP4+ probabilities and by comparison with the literature. Indicuen represents for a rare hopane bearing a 1-carboxyethyl substituent at C-21 in lichens. Compounds 1-3 and 5-8 were evaluated for α-glucosidase inhibition and cytotoxicity against K562 and HepG2 cancer cell lines. Compounds 1, 5 and 7 exhibited moderate α-glucosidase inhibition with IC50 values of 201.1, 156.3 and 187.4 µM, respectively. Compound 1 also showed weak cytotoxicity toward K562 cell line while others showed no activity.

Cycloartanes from leaves of Combretum quadrangulare growing in Vietnam.

Two new cycloartanes, combretic acid C (1) and combretanone I (3), were isolated from the leaves of Combretum quadrangulare Kurz, together with the previously-reported combretic acids A-B (2 and 5) and combretanone A (4). An extensive set of spectroscopic methods were used to elucidate the structures of these compounds. Cytotoxicity against the K562 cancer cell line was evaluated. Compound 1 showed strong activity, with an IC50 value of 9.7 µM. The other compounds showed moderate activity. Alpha-glucosidase inhibition was also evaluated. The isolated compounds showed moderate inhibition, with IC50 values in the range 102.2-194.7 µM.

Recurvataside, a new saponin from aerial parts of Mussaenda recurvata.

A new glycoside, recurvataside (1) and six known compounds, quinovic acid (2), quinovic acid 28-O-ß-D-glucopyranosyl ester (3), 3-O-ß-D-glucopyranosylquinovic acid (4), 3-O-ß-D-glucopyranosylquinovic acid 28-O-ß-D-glucopyranosyl ester (5), pomolic acid (6), and ursolic acid (7) were isolated from aerial parts of Mussaenda recurvata. The structure of compound 1 was identified from its spectroscopic data and by comparison with the literature. Recurvataside represents the first occurrence of δ-oleanolic acid saponin bearing two D-glucose units at C-3 and C-28 in nature. This is the first time δ-oleanane-type saponin reported in the genus Mussaenda. Compounds 1-7 were evaluated the cytotoxicity against two cancer cell lines MCF-7 and HepG2. Among them, only compound 7 exhibited moderate activity against MCF-7 and HepG2 cell lines with IC50 value of 16.97 ± 1.55 and 20.28 ± 1.00 µM, respectively. Compounds 1-7 were also tested for their inhibitory NO production in LPS-stimulated RAW264.7 cells. Compounds 3, 5, and 7 showed significant reduction of nitrite accumulation in LPS-stimulated RAW 264.7 cells with the IC50 values of 8.81 ± 0.48, 13.42 ± 0.84, and 18.37 ± 0.67 µM, respectively.

Lasibidoupins A and B, two new compounds from the stems of Lasianthus bidoupensis V.S. Dang & Naiki.

From the Lasianthus bidoupensis stems, two new compounds, including one new 9,10-anthraquinone, lasibidoupin A (1), and one new 6,7-benzocoumarin, lasibidoupin B (2), together with one known compound, 11-O-methyldamnacanthol (3) were isolated using chromatographic method. Their structures were determined by extensive HRMS, and NMR assignments. Compound 3 was reported for the first time from this species. New compounds (1 & 2) were tested for the cytotoxicity against three human cancer cell lines (MCF-7, HeLa, and NCI-H460) by SRB assay. As results, 1 & 2 exhibited significant cytotoxic activity against all cancer cell lines (IC50 ranged from 0.058 ± 0.003 to 0.177 ± 0.014 µM).

α-Glucosidase Inhibitory and Antimicrobial Benzoylphloroglucinols from Garcinia schomburgakiana Fruits: In Vitro and In Silico Studies.

α-Glucosidase plays a role in hydrolyzing complex carbohydrates into glucose, which is easily absorbed, causing postprandial hyperglycemia. Inhibition of α-glucosidase is therefore an ideal approach to preventing this condition. A novel polyprenylated benzoylphloroglucinol, which we named schomburgkianone I (1), was isolated from the fruit of Garcinia schomburgkiana, along with an already-reported compound, guttiferone K (2). The structures of the two compounds were determined using NMR and HRESIMS analysis, and comparisons were made with previous studies. Compounds 1 and 2 exhibited potent α-glucosidase inhibition (IC50s of 21.2 and 34.8 µM, respectively), outperforming the acarbose positive control. Compound 1 produced wide zones of inhibition against Staphylococcus aureus and Enterococcus faecium (of 21 and 20 mm, respectively), compared with the 19 and 20 mm zones of compound 2, at a concentration of 50 µg/mL. The MIC value of compound 1 against S. aureus was 13.32 µM. An in silico molecular docking model suggested that both compounds are potent inhibitors of enzyme α-glucosidase and are therefore leading candidates as therapies for diabetes mellitus.

A new eremophilane-sesquiterpene from the cultured lichen mycobiont of Graphis sp.

Lichens, a natural source producing a number of valuable compounds is economically not feasible and profitable due to its slow growth. Mycobiont cultures are alternative sources which have become highly attractive for chemists recently. Mycobiont of Graphis sp., a native lichens in Vietnam was separated then cultivated in test tubes. The present study aimed to identify chemical constituents of the cultured mycobiont of Graphis sp. Multiple chromatographic methods were applied to isolate three eremophilane sesquiterpenes including one new compound, graphilane (1) and two known compounds sporogen-AO-1 (2) and dihydrosporogen-AO-1 (3). Their chemical structures was elucidated by extensive 1 D and 2 D NMR analysis and high resolution mass spectroscopy as well as comparisons in literature. Compound 1 was evaluated for the cytotoxic activity against K562 cancer cell line and revealed moderate activity with IC50 value of 87.20 ± 0.76 µM.

A new resorcinol derivative from the bark of Aegiceras floridum (Primulaceae).

Chemical investigation of the Vietnamese plant Aegiceras floridum Roem. & Schult. (Primulaceae) led to the isolation of the new compound 3-methoxy-5-nonylphenol (1) along with five known ones 2,8,10-trihydroxy-6H-benzo[c]chromen-6-one (2), 2-hydroxy-5-methoxy-3-nonylbenzo-1,4-quinone (3), 5-(3-hydroxypropyl)-7-methoxy-3-(methylbenzofuran-2-yl)-3-methoxyphenol (4), 2,8-dihydroxy-7-methoxy-3,9-diundecyldibenzofuran-1,4-dione (5) and 10-hydroxy-4-methoxy-2,11-diundecylgomphilactone (6). The structures were elucidated by analysis of their HRESIMS and NMR data as well as the comparison of their NMR data with those reported in the literature. The cytotoxic activity of selected isolated compounds against some cancer cell lines such as human epithelial carcinoma (HeLa), human lung cancer (NCI-H460), liver hepatocellular carcinoma (HepG2), human breast cancer (MCF-7), and acute T cell leukemia (Jurkat) was evaluated. Among them, 3 showed moderate activities against MCF-7 with an IC50 of 17.77 µM and NCI-H460 with an IC50 of 25.02 µM. The result of DPPH radical scavenging activity assay indicated that compounds 2-4 and 6 revealed weak antioxidant activity.

Rukamtenol, a new spiro compound isolated from Flacourtia rukam Zoll. & Moritzi growing in Vietnam.

Chemical investigation of chloroform extract of Flacourtia rukam Zoll. & Moritzi stems led to the isolation of one new compound namely rukamtenol together with four known compounds, viz., chaulmooric acid, flacourtin, 3,4,5-trimethoxyphenyl ß-D-glucopyranoside, and daucosterol. Their structures and relative stereochemistry have been determined by 1D and 2D NMR analysis, high resolution mass spectroscopy, and compared with those in literatures. Rukamtenol represented the first 2-oxaspiro[4.4]non-8-en-3-one in nature. The relative configuration of rukamtinol was defined using DFT-NMR chemical shift calculations and subsequent DP4 probability method. Rukamtenol, flacourtin, and 3,4,5-trimethoxyphenyl ß-D-glucopyranoside were tested for cytotoxic activity toward three MDA-MB-231, HepG2, and RD cancer cell lines. However, they failed to reveal any activity (IC50 > 100 µM) on these cell lines.

Design and synthesis of new lupeol derivatives and their α-glucosidase inhibitory and cytotoxic activities.

A series of lupeol derivatives 2, 2a-2f, 2a-2h, 3a-3e, and 4a-4b were designed, synthesised and evaluated for their α-glucosidase inhibitory and cytotoxic activities. Among synthetic derivatives, lupeol analogues 2b and 2e containing a benzylidene chain exhibited the best activity against α-glucosidase and superior to the positive agent with the IC50 values of 29.4 ± 1.33 and 20.1 ± 0.91 µM, respectively. Lupeol analogues 2d and 3a showed weak cytotoxicity against K562 cell line with the IC50 values of 76.6 ± 2.40 and 94.4 ± 1.51 µM, respectively.

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.

A new 26-norlanostane from Phlogacanthus turgidus growing in Vietnam.

Chemical investigation on chloroform extract of Phlogacanthus turgidus led to the isolation of one new compound namely turgidol, together with five known triterpenoids, lupeol, lupenone, betulin, betulinic acid, and taraxerol. Their structures and stereochemistry have been determined by 1 D and 2 D NMR analysis, high resolution mass spectrometry, and compared with those in literatures. The relative configuration of turgidol was defined using DFT-NMR chemical shift calculations and subsequent DP4+ probability method. Turgidol, betulin, and betulinic acid were evaluated for cytotoxic activity toward K562 cancer cell line and the alpha-glucosidase inhibition.

A new diphenyl ether from Parmotrema indicum Hale growing in Vietnam.

Chemical investigation of the lichen Parmotrema indicum Hale led to the isolation of one new diphenyl ether, parmetherine D (1), along with eight known compounds (2-9). The structures were determined by analysis of MS and NMR data and by comparison with the literature. Compounds 1, 2, and 7 were evaluated for α-glucosidase inhibition. Only compound 1 exhibited significant inhibition.[Formula: see text].

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.

Synthesis and cytotoxic evaluation of usnic acid benzylidene derivatives as potential anticancer agents.

A series of usnic acid benzylidene derivatives (groups I-V) were designed, synthesized and evaluated for their anticancer activity in the search for potentially new anticancer agents. Compounds 1a, 5b, 2b, 2e and 2f exhibited the most potent cytotoxcity against K562 cell line with IC50 values of 10.0 ± 3.6, 5.6 ± 0.4, 8.8 ± 1.0, 4.5 ± 0.1 and 8.4 ± 0.4 µM, respectively. It is noteworthy that compound 2e displayed potent cytotoxicity against K562 cells without any cytotoxic effect on HEK293 normal cell line.

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.