Bacillus subtilis YZ-1 surfactins are involved in effective toxicity against agricultural pests.

BACKGROUND: Insect pests negatively affect crop quality and yield. The excessive use of chemical pesticides has serious impacts on the environment and food safety. Therefore, development of effective management strategies in the form of bio-agents have important agricultural applications. Tenebrio molitor, a storage pest, causes losses of grains, medicinal materials, and various agricultural and related products in the warehouse. Bacillus subtilis YZ-1 isolated from naturally deceased Pieris rapae has been found to exhibit significant toxicity against T. molitor. RESULTS: Treatment with B. subtilis YZ-1 fermentation broth resulted in a 90-95% mortality rate of T. molitor within 36 h post-treatment, indicating some active substances may have insecticidal activity in the bacterial supernatant. A bioactivity-guided fractionation method was used to isolate the insecticidal compounds from YZ-1, which led to the identification of surfactins. Additionally, a surfactin deletion mutant YZ-1△srfAA was constructed and the surfactin production by the mutant YZ-1△srfAA was verified through liquid chromatography-mass spectrometry (LC-MS). Further, YZ-1△srfAA exhibited loss of insecticidal activity against T. molitor, Plutella xylostella and Achelura yunnanensis. The insecticidal activity and surfactins contents of several strains of Bacillus sp. were also tested and correlation was found between varying surfactins yield and insecticidal activity exhibited by different strains. CONCLUSION: Conclusively, our results suggest that B. subtilis YZ-1 may provide a novel approach for plant protection against agricultural pests. © 2023 Society of Chemical Industry.

Bacillus amyloliquefaciens AK-12 Helps Rapeseed Establish a Protection against Brevicoryne brassicae.

Aphids are a serious threat to rapeseed (Brassica napus L.) production, and cause unmanageable loss. Therefore, effective prevention and management strategies are urgently required to avoid losses. Bacillus amyloliquefaciens AK-12 isolated from a dead aphid with aphicidal activity was tagged with a green fluorescent protein through a natural transformation. The transformed strains were checked for stability and growth, and the best-performing strain was tested for its colonization inside and outside the rapeseed plant. The stability of AK-12-GFP reached more than 95%, and the growth curve was consistent with that of AK-12. After 30 days of treatment, the colonization of 1 × 106 CFU/g was recorded in rapeseed leaves. Interestingly, AK-12 reduced the aphid transmission rate compared with the control and improved the growth of the rapeseed seedlings. Meanwhile, the AK-12 strain also exhibited phosphorus, potassium-solubilizing, and nitrogen-fixing activity, and produced 2.61 µg/mL of IAA at 24 h. Regulation in the activity of four enzymes was detected after the AK-12 treatment. Phenylalanine ammonia lyase (PAL) was recorded at a maximum of 86.84 U/g after 36 h, and catalase (CAT) decreased after 48 h; however, peroxidase (POD) and polyphenol oxidase (PPO) reached the maximum within 12 h of AK-12 application. Additionally, important resistance genes related to these enzymes were upregulated, indicating the activation of a defense response in the rapeseed against aphids. In conclusion, defense enzymes and defense-related gene activation could improve the pest resistance in rapeseed, which has good application prospects for the future to be developed into biopesticide.

Enhancing physical and chemical stability of hygroscopic hydroxytyrosol by cocrystal formation.

Hydroxytyrosol (HT) is a natural phenolic compound with potent antioxidant activity extracted from olive trees. It is generally a slightly hydrated viscous liquid at ambient conditions, and it is highly susceptible to oxygen due to the presence of catechol moiety. Although encapsulation technique provides HT in powder form, it does not improve its chemical stability. Herein, we propose an efficient solution to the high hygroscopicity and poor stability of HT. Four cocrystals were first reported, and their intermolecular interactions were analyzed in detail. After cocrystallization, the melting point is increased and the hygroscopicity is significantly decreased. HT cocrystals are thus solid at room temperature. Moreover, hydroxytyrosol cocrystals with betaine (HT-BET) and nicotinamide (HT-NIC) demonstrate superior chemical stability than pure HT, olive extract, and HT encapsulation material. Therefore, cocrystallization can be considered as a promising approach to overcome the application obstacles of HT.

The Cocrystal of Ubiquinol: Improved Stability and Bioavailability.

Coenzyme Q10 (CoQ10) exists in two forms, an oxidized form and a reduced form. Ubiquinol is the fully reduced form of CoQ10. Compared to the oxidized form, ubiquinol has a much higher biological absorption and better therapeutic effect. However, ubiquinol has an important stability problem which hampers its storage and formulation. It can be easily transformed into its oxidized form-ubiquinone-even at low temperature. In this work, we designed, synthesized, and characterized a new cocrystal of ubiquinol with vitamin B3 nicotinamide (UQ-NC). Compared to the marketed ubiquinol form, the cocrystal exhibited an excellent stability, improved dissolution properties, and higher bioavailability. The cocrystal remained stable for a long period, even when stored under stressed conditions. In the dissolution experiments, the cocrystal generated 12.6 (in SIF) and 38.3 (in SGF) times greater maximum ubiquinol concentrations above that of the marketed form. In addition, in the PK studies, compared to the marketed form, the cocrystal exhibited a 2.2 times greater maximum total coenzyme Q10 concentration and a 4.5 times greater AUC than that of the marketed form.

Rucaparib cocrystal: Improved solubility and bioavailability over camsylate.

Rucaparib (Ruc) is a drug used to treat advanced ovarian cancer associated with deleterious BRCA mutations. Its commercial form, the camsylate salt (Ruc-Cam), suffers from poor aqueous solubility and thus causes low and erratic oral bioavailability. In this work, we aimed to improve the oral exposure of Ruc through cocrystallization. Liquid-assisted grinding, slurry, and solvent evaporation methods were employed to prepare new solid forms of Ruc. Cocrystals of rucaparib-theophylline monohydrate (Ruc-Thp MH), rucaparib-maltol (Ruc-Mal), and rucaparib-ethyl maltol (Ruc-Emal) were obtained. Powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and dynamic vapor sorption were utilized to characterize these multi-component systems. All cocrystals dissolve faster than Ruc-Cam at pH 2.0 and 4.5, and Ruc-Thp MH displays the highest apparent solubility in pH 4.5 and 6.8 buffers. Pharmacokinetic studies in rats show that Ruc-Thp MH exhibits 2.4 times the Cmax and 1.4 times the AUC0-24h at a single dose compared with Ruc-Cam. The enhanced solubility and bioavailability of Ruc-Thp MH showcase the power of cocrystallization in addressing absorption issues in drug development.

Dehydroepiandrosterone Cocrystals with Improved Solubility and Bioavailability.

Dehydroepiandrosterone (DHEA) is an FDA-approved food supplement used as an assisted reproductive sex hormone. The bioavailability is severely limited by its poor solubility (23 µg/mL). Herein, we aimed to modulate its solubility through cocrystallization. Eight cocrystals of DHEA with pyrocatechol (CAT), hydroquinone (HQ), resorcinol (RES), phloroglucinol (PG), 1,5-dihydroxy naphthalene (DHN), p-hydroxybenzoic acid (PHBA), gallic acid (GA), and 5-hydroxyisophthalic acid (5HIPA) were designed and synthesized. Some basic characterization tools, including powder X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, and Fourier transform infrared spectroscopy, were also applied in our work for basic analyses of cocrystals. It is indicated that DHEA-GA exhibits its superiority in dissolution and pharmacokinetic behaviors. While the area under the curve values of DHEA-GA is improved at the ratio of 2.2, the corresponding bioavailability of DHEA is expected to be accordingly increased.

Bioassay-guided isolation of cytotoxic constituents from the flowers of Aquilaria sinensis.

Bioassay-guided fractionation of the EtOH extract from the flowers of Aquilaria sinensis (Lour.) Spreng. (Thymelaeaceae) led to the isolation of a new cucurbitane-type triterpenoid, aquilarolide A (1), along with five known compounds (2-6). The structure of 1 was elucidated by extensive 1D and 2D nuclear magnetic resonance (NMR) experiments and mass spectrometry (MS) data and theoretical calculations of its electronic circular dichroism (ECD) spectra. Aquilarolide A, cucurbitacin E (3), cucurbitacin B (4), and 7-hydroxy-6-methoxy-2-[2-(4-methoxyphenyl)ethyl]-4H-1-benzopyran-4-one (6) showed significant cytotoxicity against human lung adenocarcinoma SPC-A-1, human lung squamous cell carcinoma NCI-H520, human lung adenocarcinoma A549, and paclitaxel-resistant A549 (A549/Taxol) cell lines. All four active compounds, with IC50 values ranging from 0.002 to 0.91 µM, had better inhibitory activities against A549/Taxol cells than paclitaxel (IC50 = 1.80 µM). Among them, cucurbitacin E (IC50 = 0.002 µM) is the most active. Further studies are needed to evaluate their in vivo antitumor activities and to clarify their mechanisms.

Developing Penicillium digitatum Management Strategies on Post-Harvest Citrus Fruits with Metabolic Components and Colonization of Bacillus subtilis L1-21.

Citrus is among the most important plants in the fruit industry severely infected with pathogens. Citrus green mold caused by Penicillium digitatum is one of the most devastating diseases during post-harvest stages of citrus fruit. In this study, a potential endophyte Bacillus subtilis L1-21, isolated from healthy citrus plants, was assessed for its biocontrol activity against the pathogen P. digitatum. Based on an in vitro crosstalk assay, we suggested that B. subtilis L1-21 inhibits the pathogen with an inhibition zone of 3.51 ± 0.08 cm. Biocontrol efficacy was highest for the fermented culture filtrate of B. subtilis L1-21. Additionally, using GC-MS analysis, 13 compounds were detected in the extract of this endophyte. The culture filtrate in Landy medium could enlarge and deform pathogen spores and prevent them from developing into normal mycelium. Accordingly, the Landy culture filtrate of B. subtilis L1-21 was stable in the temperature range of 4-90 °C and pH of 3-11. Further, MALDI-TOF-MS for B. subtilis L1-21 detected surfactin, fengycin, bacillaene and bacilysin as potential antifungal compounds. GFP-tagged B. subtilis L1-21 easily colonized in citrus fruit peel and pulp, suggesting its role in eliminating the fungal pathogen. Altogether, it is highly expected that the production of antifungal compounds, and the colonization potential of B. subtilis L1-21 are required against the post-harvest P. digitatum pathogen on citrus fruit.

Improving the dissolution behaviors and bioavailability of abiraterone acetate via multicomponent crystal forms.

Abiraterone acetate (ABA), the first-line drug for the treatment of metastatic castration resistant prostate cancer (mCRPC), is administered at a high daily dosage of 1000 mg due to its poor solubility, and its fasted absolute oral bioavailability is estimated to be less than 10%. In this work we have focused on developing multicomponent forms with improved dissolution behaviors and bioavailability. Two salts of ABA with malonic acid (ABA-MA) and saccharin (ABA-SAC), and five cocrystals with trans-aconitic acid (ABA-TAA), 1-hydroxy-2-naphthoic acid (ABA-1HNA), pyrocatechol (ABA-PCA), resorcinol (ABA-RES) and hydroquinone (ABA-HDE) were successfully obtained. Their crystal structures were elucidated by single crystal X-ray diffraction, and these multicomponent forms were fully characterized by powder X-ray diffraction, thermal analysis and Fourier Transform Infrared spectra. Among them, ABA-TAA cocrystal shows substantial enhancements both in the solubility and intrinsic dissolution rates in different buffer solutions. In the meantime, we unexpectedly found the gelation of ABA-MA salt and ABA-SAC salt in pH 2.0 buffer solution. The gel-like materials generated on the surface of drug will suppress the release of ABA. Moreover, in vivo pharmacokinetic study on beagle dogs was conducted for ABA-TAA cocrystal preparation and ABA commercial product, and ABA-TAA cocrystal preparation shows enhanced absorption. These advantages in dissolution behaviors and bioavailability demonstrate the potential of ABA-TAA cocrystal to be a better candidate for the treatment of mCRPC compared with ABA.

Five new 2-(2-phenylethyl)chromone derivatives and three new sesquiterpenoids from the heartwood of Aquilaria sinensis, an aromatic medicine in China.

Five new 2-(2-phenylethyl)chromone derivatives, (5S,6R,7R,8S,7'R)-7'-hydroxyagarotetrol (1), (5S,6R,7R,8S,7'S)-7'-hydroxyagarotetrol (2), (6S,7S,8R)-2­[2­(4-methoxyphenyl)ethyl]­6,7,8­trihydroxy­5,6,7,8­tetrahydrochromone (3), (6S,7S,8R)-2­(2-phenylethyl)­6,7,8­trihydroxy­5,6,7,8­tetrahydrochromone (4), (5S,6R,7S,8R)-2-(2-phenylethyl)-5,6,7-trihydroxy-5,6,7,8-tetrahydro-8-[2-(2-phenylethyl)-7-methoxychromonyl-6-oxy]chromone (5), three new sesquiterpenoids, (4S,5S,7S,8S,10S,13R)-7,8,13-trihydroxyrotunda-1,11-dien-3-one (6), (4S,5S,7S,8S,10S,13S)-7,8,13-trihydroxyrotunda-1,11-dien-3-one (7), and (4R,5S,7S,8S,10S,13S)-7,8,13-trihydroxyrotunda-1,11-dien-3-one (8), along with 14 known compounds were isolated from the resinous heartwood of Aquilaria sinensis (Thymelaeaceae). The chemical structures of these new compounds were elucidated by 1D and 2D NMR and MS data, single-crystal X-ray diffraction analysis, and electronic circular dichroism (ECD) calculations. The neuroprotective activities of these isolates were evaluated using an in vitro model of rat adrenal pheochromocytoma (PC12) cell injury induced by corticosterone. At concentrations from 5 to 40 µM, compounds 4 and 6, agarotetrol (9), and 6-hydroxy-2-(2-phenylethyl)chromone (17) showed significant protective activities against corticosterone-induced PC12 cell injury (P < 0.001).

Conformational polymorphs of isotretinoin and their impact on physicochemical and biological properties.

Isotretinoin is the first-line drug for treatment of severe acne. Only one polymorph was reported even though it has been launched for nearly 40 years, and its clinic application was however limited by its stability and solubility challenges. In our study, two new polymorphs of isotretinoin were discovered and fully characterized. The transformation relationships between these solid forms were fully discussed, and a visible color change during single-crystal-to-single-crystal phase transition with the conformational change was investigated. Form II is determined to be thermodynamic stable form at room temperature, but metastable form at body temperature. The results show that form II is an ideal solid state possessing both superior thermal stability (60℃, open air) and higher absorption once delivered into body. The thermal stability can be associated with the crystal structure such as torsion angle. The relative bioavailability of form II is higher than form I as expected, and the bioavailability of form II formulation is about 2 times as that of the marketed form I capsule. Therefore, form II formulation could provide an alternative for better performing isotretinoin.

Bacillus amyloliquefaciens YN201732 Produces Lipopeptides With Promising Biocontrol Activity Against Fungal Pathogen Erysiphe cichoracearum.

Bacillus amyloliquefaciens YN201732 is an endophytic bacteria with high biocontrol efficiency and broad-spectrum antimicrobial activities. In order to clarify the main active ingredients and their antifungal mechanisms against powdery mildew of tobacco, this study is focused on lipopeptide obtained through acid precipitation and organic solvent extraction. HPLC and LCMS-IT-TOF were used to separate and identify antimicrobial lipopeptides. Findings revealed that bacillomycin D plays an important role against surrogate fungal pathogen Fusarium solani. Synthetic pathways of sfp, bacillomycin D, and fengycin were separately disrupted. The sfp gene knockout mutant B. amyloliquefaciens YN201732M1 only showed minor antagonistic activity against F. solani. While Erysiphe cichoracearum spore germination was inhibited and pot experiments displayed a significant decrease in tobacco powdery mildew. The spore inhibition rate of YN201732M1 was only 30.29%, and the pot experiment control effect was less than 37.39%, which was significantly lower than that of the wild type. The inhibitory effect of mutant YN201732M2 (deficient in the production of bacillomycin D) and mutant YN201732M3 (deficient in the production of fengycin) on the spore germination of E. cichoracearum were 50.22% and 53.06%, respectively, suggesting that both fengycin and bacillomycin D had potential effects on spore germination of powdery mildew. Interestingly, in a greenhouse assay, both B. amyloliquefaciens YN201732M2 and YN201732M3 mutants displayed less of a control effect on tobacco powdery mildew than wild type. The results from in vitro, spore germination, and greenhouse-pot studies demonstrated that antimicrobial lipopeptides especially bacillomycin D and fengycin may contribute to the prevention and control of tobacco powdery mildew. In addition, gene mutation related to lipopeptide synthesis can also affect the biofilm formation of strains.

Sesquiterpenoids and 2-(2-Phenylethyl)chromone Derivatives from the Resinous Heartwood of Aquilaria sinensis.

One novel spirolactone, aquilarisinolide (1), three new sesquiterpenoids, (2R,4S,5R,7R)-2-hydroxyeremophila-9,11-dien-8-one (2), (1R,4S,5S,7R,11R)-13-hydroxyepidaphnauran-9-en-8-one (3), and (4R,5S,7R,8S,10S,13R)-8,13-dihydroxyrotunda-1,11-dien-3-one (4), together with 13 known compounds (5-17) were isolated from the resinous heartwood of Aquilaria sinensis (Thymelaeaceae). The structures of the new compounds were elucidated based on the analysis of NMR and MS data and theoretical calculations their ECD spectra. The isolated compounds were evaluated for their protective activities against PC12 cell injury induced by corticosterone (CORT) and 1-methyl-4-phenylpyridine ion (MPP+), as well as inhibitory activities against BACE1. Compound 4, 5,6-dihydroxy-2-(2-phenylethyl)chromone (5), daphnauranol B (7), 6-methoxy-2-[2-(3-methyoxyphenyl)ethyl]chromone (10), isoagarotetrol (14), and 1-hydroxy-1,5-diphenylpentan-3-one (16) showed significant protective effects on CORT-induced injury in PC12 cells at a concentration of 20 µM (P < 0.001). Isoagarotetrol (14) showed a significant protective effect on MPP+-induced injury in PC12 cells at a concentration of 20 µM (P < 0.001), while compound 4 showed a moderate activity (P < 0.01). The BACE1-inhibitory activities of all tested compounds were very weak with less than 30% inhibition at a concentration of 20 µM.

A new sesquineolignan and four new neolignans isolated from the leaves of Piper betle, a traditional medicinal plant in Myanmar.

One new sesquineolignan, piperneolignan A (1), four new neolignans, piperneolignans B-E (2-5), and eight known compounds were isolated from the leaves of Piper betle (Piperaceae) collected from Myanmar. These new structures were determined by analysis of MS and NMR data, and the absolute configuration of piperneolignan A was elucidated by electronic circular dichroism (ECD) calculations. Piperneolignan A (1), piperneolignan B (2), hydroxychavicol (6), p-hydroxycinnamaldehyde (10), and diallylcatechol (13) possessed anti-inflammatory activity against nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells with IC50 values of 9.87, 45.94, 4.80, 26.40, and 40.45 µM, respectively, compared with the positive control NG-monomethyl-l-arginine (l-NMMA, IC50 = 33.84 µM). The two hydroxy groups in the structure of hydroxychavicol are essential for activity, and dimerization or trimerization of hydroxychavicol decreases activity.

Neuroprotective compounds from the resinous heartwood of Aquilaria sinensis.

Six undescribed compounds, including three sesquiterpenoids [(4S,5S,7S,8S,11R)-7-hydroxyguai-1(10)-en-8,12-olide, aquilarisinone, and 2Z,7(13),9E-humulatrien-12-ol-5-one], one diphenylpentanone [1-(2-hydroxyphenyl)-5-phenylpentan-3-one], and two 2-(2-phenylethyl)chromones (6-epiagarotetrol and triepoxyhexahydrochromone A), along with 15 known compounds, were isolated from the resinous heartwood of Aquilaria sinensis (Thymelaeaceae). Their structures were determined by mass (MS) and nuclear magnetic resonance (NMR) spectroscopic data. The absolute configuration of (4S,5S,7S,8S,11R)-7-hydroxyguai-1(10)-en-8,12-olide was confirmed by X-ray diffraction analysis, and the configurations of (4S,7S,8S,10R,11R)-7,10-epoxyguai-1(5)-en-8,12-olide, aquilarisinone, 6-epiagarotetrol, and triepoxyhexahydrochromone A were confirmed by electronic circular dichroism (ECD) calculations. The neuroprotective activities of the compounds were evaluated using models of BACE1 inhibition and PC12 cells with corticosterone- and 1-methyl-4-phenylpyridine ion (MPP+)-induced damage. At concentrations of 1, 2, and 5 µM, triepoxyhexahydrochromone A, (+)-(7R,10R)-selina-4,11(13)-diene-12,15-dial, (-)-(5R,7R,10R)-12,15-dioxo-α-selinene, and (+)-(1R,4S,5R)-1ß-hydroxyeremophila-7(11),9-dien-8-one exerted significant protective effects (p < 0.01) on PC12 cell injury induced by corticosterone, while triepoxyhexahydrochromone A and (-)-(5R,7R,10R)-12,15-dioxo-α-selinene exerted significant protective effects (p < 0.01) on MPP+-induced PC12 cell injury at concentrations of 1, 2, and 5 µM. No compounds produced significant inhibitory effects on BACE1, with inhibition rates of less than 20% observed at a concentration of 20 µM.

Chemical Constituents from the Whole Plant of Cuscuta reflexa.

Two new 2H-pyran-2-one glucosides, cuscutarosides A (1) and B (2), and one new steroidal glucoside, 7ß-methoxy-ß-sitosterol 3-O-ß-glucopyranoside (3), together with 12 known compounds (4-15) were isolated from the whole plant of Cuscuta reflexa (Convolvulaceae) collected from Myanmar. The chemical structures of these new compounds were elucidated based on extensive spectroscopic analysis. The antiobesity activity of these isolates was evaluated using porcine pancreatic lipase (PPL), and the antiplatelet aggregation activity was screened using rabbit platelets induced by thrombin, platelet-activating factor (PAF), arachidonate (AA), or collagen. 7ß-Methoxy-ß-sitosterol 3-O-ß-glucopyranoside (3) showed weak PPL inhibitory activity. Cuscutaroside A (1), its acetylated derivative (1a), and scrophenoside B (8) showed weak inhibitory activity against rabbit platelet aggregation induced by collagen. Compound 1a also showed inhibitory activity against rabbit platelet aggregation induced by AA.

Total saponins from Paris forrestii (Takht) H. Li. show the anticancer and RNA expression regulating effects on prostate cancer cells.

Paris forrestii is a unique plant found in Tibet and Yunnan, China, and total saponins from Paris forrestii (PCT3) contain anticancer steroid glycosides. RNA expression plays an important role in various biological processes. However, the cytotoxicity effects and mechanisms of PCT3 in relation to prostate cancer (PCa) cells have not yet been reported. In the present study, the antitumor activity of PCT3 on PCa cells was evaluated. PCT3 displayed potent anticancer effects toward PCa cells that were similar to the effects of pure saponins from P. forrestii, but PCT3 had less activity in suppressing the prostate epithelial cell line RWPE. Furthermore, using CCK-8 assays, Edu incorporation, colony formation assays, Annexin V/PI assays and western blotting, we found that treatment with 4 µg/mL PCT3 significantly decreased proliferation and induced apoptosis in PCa cells. Using wound healing and transwell assays, we demonstrated that treatment with 2 µg/mL PCT3 significantly suppressed the migration and invasion of PCa cells. To explore the molecular mechanisms behind the anticancer effect of PCT3, PCT3 (5 µg/mL) treated and untreated PCa cells (LNCAP and PC3 cell lines) were analyzed using transcriptomics. Taking the commonly differentially expressed genes (log2FC > 0.585) in both cell lines, 41 mRNAs and 5 lncRNAs were eventually identified. Bioinformatics analysis (GO and KEGG analyses) revealed that some genes involved in classical cell proliferation and apoptosis pathways were aberrantly expressed after PCT3 treatment of PCa cells. By using q-PCR, the expression levels of NEAT1, MALAT1, TIPIN, LYAR, IQGAP3, GINS2, and ZGRF1 were validated as consistent with microarray data, suggesting that these genes might participate in the PCT3 anticancer effect. The present study suggests that PCT3 exhibits an anticancer effect on PCa and reveals some crucial lncRNAs and mRNAs that are involved in the anticancer mechanisms of PCT3 on Pca.

Alkaloids from the Branches and Leaves of Elaeocarpus angustifolius.

Nine new alkaloids, (+)-1, (-)-1, 2, (+)-3, (-)-3, and 4-7, along with five known compounds (8-12), were obtained from the branches and leaves of Elaeocarpus angustifolius. The alkaloids were structurally characterized by NMR and MS data. The absolute configurations of (+)-1, (-)-1, (+)-3, and (-)-3 were determined by comparing their experimental and computed electronic circular dichroism spectra. (±)-8,9-Dehydroelaeocarpine (5), (±)-9-epielaeocarpine cis-N-oxide trifluoroacetate (6), and (±)-elaeocarpine trifluoroacetate (9) exerted weak inhibitory activities against butyrylcholinesterase with IC50 values of 39, 29, and 35 µM, respectively, while that of tacrine, the positive control, was 0.07 ± 0.01 µM. This is the first report of the cholinesterase inhibitory activities of Elaeocarpus alkaloids.

Chemical Constituents from Ethanoic Extracts of the Aerial Parts of Leea aequata L., a Traditional Folk Medicine of Myanmar.

We aimed at reporting the chemical constituents and antimicrobial activities of Leea aequata L., a traditional folk medicine used in Myanmar for the treatment of wounds and skin diseases. A new neolignan, (7S,8R)-9'-O-acetylcedrusin (1), a new lactam, (3S,4S)-4-chloro-3-hydroxypiperidin-2-one (2), along with 21 known compounds, including five lignans (3-7), four flavonoid glycosides (8-11), and others (12-23), were isolated from the ethanoic extract of the aerial parts of L. aequata. The structures of the new compounds were determined by NMR, MS, and ECD spectra. For all the antimicrobial tests of the 23 compounds, only 3,4,5-trihydroxybenzoic acid ethyl ester (17) showed weak inhibitory activities against Escherichia coli and Salmonella enterica subsp. enterica.

Amides, Isoquinoline Alkaloids and Dipeptides from the Aerial Parts of Piper mullesua.

One undescribed amide, pipermullesine A, two undescribed isoquinoline alkaloids, pipermullesines B and C, and six undescribed dipeptides, pipermullamides A-F, along with 28 known compounds, were isolated from the aerial parts of Piper mullesua. The structures of the undescribed compounds were elucidated based on the analysis of 1D and 2D NMR and MS data. Furthermore, the structures of pipermullesines A-C were confirmed by single crystal X-ray diffraction analysis. All isolates were evaluated for inhibitory activity against platelet aggregation induced by thrombin (IIa) or platelet-activating factor (PAF). (-)-Mangochinine, pellitorine, and (2E,4E)-N-isobutyl-2,4-dodecadienamide showed weak inhibitory activity against rabbit platelet aggregation induced by PAF, with IC50 values of 470.3 µg/mL, 614.9 µg/mL, and 579.7 µg/mL, respectively.