Tetrahydroxanthene-1,3(2H)-diones and Oxidized Hexadiene Derivatives from Uvaria leptopoda and Their Biological Activities.

The first phytochemical investigation of the twig extract of Uvaria leptopoda resulted in the isolation and identification of three new tetrahydroxanthene-1,3(2H)-diones, uvarialeptones A-C, two new oxidized hexadiene derivatives, uvarialeptols A and B, together with ten known compounds. Their structures were elucidated by spectroscopic techniques and mass spectrometry. Uvarialeptones A and B were unprecedented tetrahydroxanthene-1,3(2H)-dione dimers which exhibited a cyclobutane ring via [2 + 2] cycloaddition from uvarialeptone C and 9a-O-methyloxymitrone, respectively. The structure of uvarialeptone A was confirmed by X-ray diffraction analysis using Mo Kα radiation. Compound 3 inhibited NO production at an IC50 value of 6.7 ± 0.1 µM.

Alkaloids and Styryl lactones from Goniothalamus ridleyi King and Their α-Glucosidase Inhibitory Activity.

Gonioridleylactam (1), a new compound, is a unique dimeric aristolactam isolated from the EtOAc extract of the twigs of Goniothalamus ridleyi King. The structure of gonioridleylactam (1) consists of two different aristolactams linked together with two methylenedioxy bridges at C-3/C-3' and C-4/C-4', generating a ten-membered ring of [1,3,6,8]tetraoxecine. A new natural product, gonioridleyindole (3-hydroxymethyl-1-methyl-1H-benz[f]indole-4,9-dione, 2), together with eight known compounds (3-10) were also isolated from this plant. Their structures were extensively characterized by spectroscopic methods and comparisons were made with the literature. Compounds 1-4, 7, and 9 were evaluated for their α-glucosidase inhibitory activity. Of these, 3,5-demethoxypiperolide (7) displayed the highest α-glucosidase inhibitory activity, with an IC50 value of 1.25 µM.

Kaempferia parviflora Rhizome Extract as Potential Anti-Acne Ingredient.

Kaempferia parviflora (Black ginger) is used widely in medical fields as an anti-microorganism and anti-inflammation. In this study, the aim was to evaluate the in vitro and in vivo anti-acne efficacy of black ginger extract. The results indicate that the methanol and ethanol extracts showed the highest total phenolic contents, without a significant difference, whereas the n-hexane extract showed the highest total flavonoid content. Nine flavones were detected using UPLC-QTOF-MS, and the ethyl acetate extract showed the highest amount of 5,7-dimethoxyflavone (DMF) according to HPLC. Antibacterial activity against Staphylococcus aureus, S. epidermidis, and Cutibacterium acnes was observed. All the extracts showed antimicrobial activity against C. acnes, revealing MICs in the range of 0.015 to 0.030 mg/mL, whereas the ethyl acetate extract inhibited the growth of S. epidermidis with a MIC of 3.84 mg/mL. In addition, the ethyl acetate extract showed the highest activity regarding nitric oxide inhibition (IC50 = 12.59 ± 0.35 µg/mL). The ethyl acetate extract was shown to be safe regarding cell viability at 0.1 mg/mL. The anti-acne efficacy was evaluated on volunteers. The volunteers were treated in two groups: one administered a 0.02% ethyl acetate extract gel-cream (n = 9) and one administered a placebo (n = 9) for 6 weeks. The group treated with the gel-cream containing the extract showed 36.52 and 52.20% decreases in acne severity index (ASI) after 4 and 6 weeks, respectively, and 18.19 and 18.54% decreases in erythema, respectively. The results suggest that K. parviflora could be a potent active ingredient in anti-inflammatory and anti-acne products.

Aporphine alkaloids and a naphthoquinone derivative from the leaves of Phaeanthus lucidus Oliv. and their α-glucosidase inhibitory activity.

Three previously undescribed aporphine alkaloids, phaeanthuslucidines E-G, one previously undescribed naphthoquinone derivative, phaeanthusnaphthoquinone, and three known compounds were isolated from an EtOAc extract of the leaves of Phaeanthus lucidus Oliv. The structures of all previously undescribed compounds were established through extensive spectroscopic investigations and high-resolution mass spectroscopy. The 6aR configuration of phaeanthuslucidines E-G was assigned by comparing their ECD spectra and specific rotation values with the reported known compounds. Some isolated compounds were evaluated for their α-glucosidase inhibitory activity. Among these compounds, phaeanthuslucidine E showed the highest α-glucosidase inhibitory activity with an IC50 value of 17.9 ± 0.4 µM. The molecular docking of phaeanthuslucidine E was further studied.

Styryl lactone derivatives and aristolactam alkaloids from Goniothalamus tapis Miq. and their α-glucosidase inhibitory activity.

Two new styryl lactone derivatives, goniothapic acids A (1) and B (2), and 18 known compounds, were isolated from the twig and leaf extracts of Goniothalamus tapis Miq. The structures of new compounds were characterised by spectroscopic methods and HRESITOFMS. Their absolute configuration was established by comparing the experimental and calculated ECD spectra. Eleven compounds were evaluated for their α-glucosidase inhibitory activity. Of these, (-)-goniothalamin (5) and oldhamactam (16) showed the best α-glucosidase inhibitory activity with IC50 values of 54.8 and 57.9 µM, respectively.

Highly oxygenated cyclohexenes from Uvaria dac Pierre ex Finet & Gagnep. and their α-glucosidase inhibitory activity.

Phytochemical investigations of the twig and leaf extracts of Uvaria dac Pierre ex Finet & Gagnep. resulted in the isolation and identification of five new highly oxygenated cyclohexenes, uvaridacols M - Q (1-3, 5, and 6), and six known compounds (4 and 7-11). All new structures were elucidated by spectroscopic methods and HRESITOFMS data. The absolute configuration of 1, 5, and 6 was confirmed by single X-ray diffraction analysis with Cu Kα radiation. In contrast, other compounds were established by comparing their specific rotation and ECD spectra with those of known compounds. Some of the isolated compounds with sufficient quantity were evaluated for their α-glucosidase inhibitory activity. Of these, (-)-1,6-desoxypipoxide (10) showed α-glucosidase inhibitory activity with an IC50 value of 28.6 µM. The in silico molecular docking of active compounds was also studied.

Xanthones from the latex and twig extracts of Garcinia nigrolineata Planch. ex T. Anderson (Clusiaceae) and their antidiabetic and cytotoxic activities.

A new geranylated xanthone, nigrolineaxanthone AA (1) together with 18 known compounds (2-19) were isolated from latex and twig extracts of Garcinia nigrolineata Planch. ex T. Anderson. Some of the isolated compounds were assessed for their antidiabetic activities and cytotoxicity against three cancer cell lines. Of these, compounds 12 (IC50 value of 25.8 ± 0.2 µM), 16 (IC50 value of 124.8 ± 0.7 µM), and 17 (IC50 value of 44.4 ± 1.1 µM) exhibited the highest α-glucosidase inhibitory, α-amylase inhibitory, and glycation inhibition activities, respectively. Compound 11 showed glucose consumption and glucose uptake with IC50 values of 14.2 ± 0.8 µM and 3.1-fold. Compound 10 displayed cytotoxic activity against colon cancer (SW480) with an IC50 value of 4.3 ± 0.1 µM), while compound 2 showed cytotoxicity against leukemic cancer (K562) with IC50 value of 4.4 ± 0.3 µM.

Phaeanthuslucidines A-D, dimeric aporphine alkaloid derivatives from Phaeanthus lucidus Oliv.

The first phytochemical investigation of the twigs of Phaeanthus lucidus Oliv. resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. Their structures were determined by extensive analysis of spectroscopic data, and by comparison of their spectroscopic and physical data with previous reports. Phaeanthuslucidines A-C and bidebiline E were analysed and resolved by chiral HPLC to yield the (Ra) and (Sa) atropisomers, whose absolute configurations were respectively determined by ECD calculations. Phaeanthuslucidines A and B, bidebiline E, and lanuginosine showed α-glucosidase inhibitory activities with IC50 values in the range of 6.7-29.2 µM. Moreover, molecular docking simulations of α-glucosidase inhibition of active compounds were studied.

Dimeric aporphine alkaloids from the twigs of Trivalvaria costata (Hook.f. & Thomson) I.M.Turner.

A phytochemical investigation of the twig extract of Trivalvaria costata (Hook.f. & Thomson) I.M.Turner has identified ten undescribed dimeric aporphine alkaloids, trivalcostatines A-J, one undescribed isoquinoline alkaloid, trivalcostaisoquinoline, and four known aporphine alkaloids. Their structures were elucidated by detailed analysis of NMR and HRESITOFMS data. Three of the dimeric aporphine structures were confirmed by single crystal X-ray diffraction analysis. All of the dimeric aporphine alkaloids were isolated as mixtures of atropisomers. Several of them were resolved by chiral-phase HPLC and the absolute configurations of the pure atropisomers were assigned by calculated and experimental ECD analysis. Bidebilines A and B, heteropsine, and urabaine showed α-glucosidase inhibitory activities with IC50 values in the range of 4.1-11 µM.

α-Glucosidase inhibitory and α-amylase inhibitory activities of compounds isolated from Uvaria rufa Blume.

A new C-benzylated flavone, uvariaruflavone (1), along with 13 known compounds (2-14) were isolated from the twig and leaf extracts of Uvaria rufa Blume. Their structures were established by extensive spectroscopic methods. Flavones (5-8) and cyclohexene (10) were isolated from U. rufa for the first time. Most of the isolated compounds were evaluated for their α-glucosidase and α-amylase inhibitory activities. Of these, uvariaruflavone (1) showed the highest α-glucosidase inhibitory activity with an IC50 value of 44.3 µM, while ferrudiol (12) displayed the highest α-amylase inhibitory activity with an IC50 value of 73.5 µM.

Nitric oxide production inhibitory activity of clerodane diterpenes from Monoon membranifolium.

A new clerodane diterpene, 2ß-methoxyhardwickiic acid (1), and four known compounds (2-5) were isolated from the twigs of Monoon membranifolium. The structure of the new compound was determined by extensive spectroscopic methods and ESITOFMS data. The absolute configuration of 1 was established by a comparison of its ECD spectrum and specific rotation with those of related previously reported compounds. All compounds were evaluated for their nitric oxide (NO) production inhibitory activities in RAW264.7 macrophage cells. Compounds 3 and 5 inhibited NO production with IC50 values of 16.1 and 28.9 µM, respectively, which were better than that of standard compound, indomethacin (IC50 = 32.2 µM).

Special Thai Oolong Tea: Chemical Profile and In Vitro Antidiabetic Activities.

Special Thai oolong tea is oolong tea (Camellia sinensis (L.) Kuntze) steamed with selected Thai botanical drugs. Oolong tea steamed with ginger (Zingiber officinale), lemongrass (Cymbopogon citratus), and celery (Anathallis graveolens L.) is called eternity tea (EN), whereas peaceful rest (PR) tea is made of oolong tea leaves steamed with Indian gooseberry (Phyllanthus emblica), Turkey berry (Solanum torvum), and wild betel leaf bush leaves (Piper sarmentosum). Oolong tea is known for its numerous biological activities including antidiabetic properties. However, the effect of the additional botanical drugs on the biological activities of special oolong teas has not yet been explored. From the results, the PR extract exhibited the best activity in the in vitro assays relevant to antidiabetic properties such as chemical antioxidant, anti-inflammation, anti-adipogenesis, enzyme inhibition, and glucose uptake and consumption. The UHPLC-QTOF-MS/MS profiles of PR and EN extracts indicated chemical profiles different from oolong tea. For instance, gingerdiol and gingerol were detected in EN, whereas piperettine I was detected in PR. Therefore, it was inferred that among the three tea extracts, the additional compounds in PR contributed to good activities compared to oolong and EN. It is also important to highlight that the PR extract inhibited glucose uptake and consumption by adipocytes and skeletal muscles at concentrations of 500 and 100 µg/ml, respectively, as well as metformin activity (p < 0.05). Findings from this study support the antidiabetic potential of PR tea.

Antidiabetic and Cytotoxic Activities of Rotenoids and Isoflavonoids Isolated from Millettia pachycarpa Benth.

A phytochemical investigation of the root and leaf extracts of Millettia pachycarpa Benth resulted in the isolation and identification of 16 compounds, including six rotenoids (1-6) and 10 prenylated isoflavonoids (7-16). Compound 4 was isolated as a scalemic mixture, which was resolved by chiral HPLC to afford (-)-(6aS,12aS)-12a-hydroxy-α-toxicarol (4) and (+)-(6aR,12aR)-12a-hydroxy-α-toxicarol (4). (+)-(6aR,12aR)-Millettiapachycarpin (3) and (-)-(6aS,12aS)-12a-hydroxy-α-toxicarol (4) were isolated as new compounds. The absolute configuration of (-)-(6R)-pachycarotenoid (2), (+)-(6aR,12aR)-millettiapachycarpin (3), (-)-(6aS,12aS)-4 and (+)-(6aR,12aR)-12a-hydroxy-α-toxicarol (4), (+)-(6aS,12aS)-(5), and (-)-(6aS,12aS,2″R)-sumatrol (6) were identified by electronic circular dichroism (ECD) data. (-)-(6aS,12aS,2″R)-Sumatrol (6) was also confirmed by X-ray diffraction analysis using Cu-Kα radiation. Antidiabetic activities, including α-glucosidase and α-amylase inhibitory activities, and cytotoxicities against lung cancer A549, colorectal cancer SW480, and leukemic K562 cells of some isolated compounds were evaluated. Of these, isolupalbigenin (11) exhibited the highest α-glucosidase inhibitory activity, with an IC50 value of 11.3 ± 0.2 µM, whereas the scalemic mixture of 12a-hydroxy-α-toxicarol (4) displayed the best α-amylase inhibitory activity, with an IC50 value of 106.9 ± 0.2 µM. Euchrenone b10 (15) exhibited the highest cytotoxicity against lung cancer A549, colorectal cancer SW480, and leukemic K562 cells, with IC50 values of 40.3, 39.1, and 15.1 µM, respectively. In addition, molecular docking simulations of α-glucosidase inhibition of the active compounds were studied.

Rotenoids and isoflavones from the leaf and pod extracts of Millettia brandisiana Kurz.

Phytochemical investigations of the leaf and pod extracts of Millettia brandisiana Kurz led to the isolation and identification of four previously undescribed rotenoids, (-)-(6aS,12aS)-millettiabrandisins A-C and (-)-(6aS,12aS)-6-deoxyclitoriacetal, two previously undescribed isoflavones, millettiabrandisins D and E, and 20 known compounds. The structures of previously undescribed compounds were determined on the basis of NMR and MS data. The absolute configurations of (-)-(6aS,12aS)-millettiabrandisins A-C were determined from the comparison of their experimental and calculated ECD spectra. (-)-(6aR,12aR)-12a-Hydroxy-α-toxicarol was also confirmed by X-ray crystallographic data. Some isolated compounds were evaluated for their cytotoxicity against three cancer cell lines, including lung cancer (A549), colorectal cancer (SW480), and leukemic cells (K562). Of these, α-toxicarol displayed the best cytotoxicity against lung cancer (A549) and leukemic cells (K562) with the IC50 values of 104.4 and 67.5 µM, respectively. 6″,6″-Dimethylchromene-[2″,3″:7,8]-flavone showed the highest cytotoxicity against colorectal cancer (SW480) with an IC50 value of 97.2 µM.

α-Glucosidase inhibitory activity of compounds isolated from the twig and leaf extracts of Desmos dumosus.

Four new compounds, (+)-(2S)-desmosdumosone (1), (+)-(2R)-7,8-dimethoxy-5-hydroxyflavanone (7), (+)-(2R)-7-methoxychamanetin (9), and (+)-(1'R,2'R)-phebalosin (18), and 25 known compounds were isolated from the twig and leaf extracts of Desmos dumosus. Compounds (±)-7 and (±)-9 were isolated as racemates and their enantiomers were separated by chiral HPLC. Their structures were elucidated by spectroscopic methods as well as comparisons made from the literature. The absolute configuration of (+)-(1'R,2'R)-18 was established by X-ray diffraction analysis using Cu Kα radiation and electronic circular dichroism (ECD) spectoscopy. In contrast, the absolute configuration of compounds (+)-(2S)-1, (+)-(2R)-7, and (+)-(2R)-9 were identified by comparing their ECD spectra and specific rotations with those of reported known compounds. Compounds 9, 11, 13, 14, 22, 25, and 28 showed α-glucosidase inhibitory activities with IC50 values ranging from 5.3-52.7 µM, much better than that of standard control (acarbose, IC50 value 83.5 µM). Compound 13 was the most active with an IC50 value of 5.3 µM.

Macluracochinones A-E, antimicrobial flavonoids from Maclura cochinchinensis (Lour.) Corner.

The phytochemical investigation of the fruit and leaf extracts of Maclura cochinchinensis (Lour.) Corner (Moraceae) resulted in the isolation and identification of four undescribed isoflavones (macluracochinones A-D) and one undescribed flavone (macluracochinone E), together with 24 known compounds. The structures of the undescribed compounds were elucidated using nuclear magnetic resonance (NMR) and high-resolution electrospray ionization time-of-flight mass spectrometry (HRESITOFMS) experiments. Gancaonin M, lupiwighteone, lupalbigenin, warangalone, auriculatin, and millexatin F displayed good antibacterial activities against Gram-positive bacteria with MIC values in the range of 1-8 µg/mL. Lupalbigenin showed strong activities against methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus with the same MIC value of 1 µg/mL.

Antidiabetic and antimicrobial flavonoids from the twigs and roots of Erythrina subumbrans (Hassk.) Merr.

The phytochemical investigation of the twig and root extracts of Erythrina subumbrans (Hassk.) Merr. (Fabaceae) resulted in the isolation and identification of a new pterocarpan, erythrinocarpan (1), along with 27 known compounds (2-28). All isolated compounds were evaluated for their antidiabetic, antimicrobial, and anti-inflammatory properties. Compounds 3, 8, 9, and 22 had α-glucosidase inhibitory activity with IC50 values of 13.4 ± 0.05, 24.5 ± 0.13, 29.0 ± 0.05, and 12.8 ± 0.14 µM, respectively, while compound 2 inhibited α-amylase activity with an IC50 value of 67.6 ± 1.12 µM. Compounds 22 and 24 inhibited glycation activity with the IC50 values of 36.9 ± 0.62 and 40.5 ± 0.37 µM, respectively. From cell-based assays, compound 27 showed the highest ability to induce glucose consumption (IC50 29.1 ± 0.86 µM) and glucose uptake (2.8-fold), and to inhibit nitric oxide (NO) production (IC50 52.5 ± 0.56 µM) without cell toxicity. Furthermore, compound 9 showed antimicrobial activities against Gram-positive bacteria and fungi with MIC values ranging from 2-4 µg/mL.

Cytotoxicity and Nitric Oxide Production Inhibitory Activities of Compounds Isolated from the Plant Pathogenic Fungus Curvularia sp.

Chemical investigation of the mycelia of the pathogenic fungus Curvularia sp. which was isolated from a leaf of Dactyloctenium aegyptium (crowfoot grass), resulted in the isolation of a new compound, curvulariahawadride (5), along with five known compounds (1-4, and 6). Their structures were determined on the basis of spectroscopic data, including 1D and 2D NMR and HRESIMS. The absolute configuration of 5 was established from experimental and calculated electronic circular dichroism (ECD). Compounds 1, 3, and 5 showed nitric oxide (NO) production inhibitory activity with IC50 values of 53.7, 32.8, and 12.8 µM, respectively. Compounds 2 and 4 showed significant cytotoxicity against lung cancer A549, colorectal cancer SW480, and leukemic K562 cells with an IC50 ranging value of 11.73 to 17.59 µM.

Daldiniaeschsone A, a Rare Tricyclic Polyketide Having a Chromone Unit Fused to a δ-Lactone and Its Symmetrical Biphenyl Dimer, Daldiniaeschsone B, from an Endophytic Fungus Daldinia eschscholtzii SDBR-CMUNKC745.

Daldiniaeschsone A (1), a rare tricyclic polyketide having a chromone unit fused to a δ-lactone and its symmetrical 6,6'-biphenyl dimer, daldiniaeschsone B (2), together with three known compounds (3-5), were isolated from a plant-derived endophytic fungus, Daldinia eschscholtzii SDBR-CMUNKC745. Their structures were elucidated by extensive 1D and 2D NMR spectroscopic data and HRESIMS. All compounds showed α-glucosidase inhibitory activity with IC50 values ranging from 0.16-0.85 mM and compound 1 was the best α-glucosidase inhibitory activity (IC50 = 0.16 mM).

Desmoschinensisflavones A and B, two rare flavones having a hybrid benzyl benzoate ester-flavone structural framework from Desmos chinensis Lour.

Two rare flavones having a hybrid benzyl benzoate ester-flavone structural framework, desmoschinensisflavones A and B (1 and 2), together with 12 known compounds (3-14) were isolated from the fruit, leaf, and twig extracts of Desmos chinensis (red flower). The new structures were characterized by UV, IR, NMR, and HRESITOFMS data. Desmoschinensisflavones A and B have a distinctive skeleton of benzoate ester-flavones with a C-4'' and C-6 and C-8 connection via a methylene group, respectively. Plausible biosynthesis pathways to compounds 1 and 2 are proposed based on an intermolecular nucleophilic 1,4-addition to ortho-quinone intermediates. Compounds 6-8 and 12 showed weakly antioxidant inhibition with IC50 values in the range of 65.4-74.6 µM.