Isolation,characterization and acetylcholinesterase inhibitory activity of alkaloids from roots of Stemona sessilifolia

Two new alkaloids, named stenine A (1) and stenine B (2), along with the known compounds neostenine (3), stenine (4) and neotuberostemonine (5), were isolated from the roots of Stemona sessilifolia. Their structures were elucidated by 1D- and 2D-NMR spectra and X-ray single-crystal diffraction experiment. Anti-acetylcholinesterase (AChE) activity of compounds 1–5 were also tested. Compounds 2 and 4 showed significant anti-acetylcholinesterase activities, with IC₅₀ values of 2.1 ± 0.2 μM and 19.8 ± 2.5 μM, resp. The mode of AChE inhibition by Compound 2 (the most potential AChE inhibitor) was reversible and competitive. In addition, molecular modeling was performed to explore the binding mode of compound 2 with AChE.     

Carapanolides C–I from the seeds of andiroba (Carapa guianensis,Meliaceae)

Five new mexicanolide-type limonoids, carapanolides C–G (1–5), together with two new phragmalin-type limonoids, carapanolides H–I (6, 7), were isolated from the oil of Carapa guianasis AUBLET (Meliaceae) seeds. Their structures were elucidated on the basis of spectroscopic analyses using 1D and 2D NMR spectra and FABMS. Carapanolides C (1), E (3), and I (7) exhibited moderate activity in the P388 (IC₅₀ 17.9 μM in 1, 15.8 μM in 3) and L1210 cell lines (IC₅₀ 13.3 μM in 1, 18.1 μM in 3, 16.9 μM in 7). On the other hand, Carapanolide D (2) exhibited a strong inhibitory effect in the HL-60 cell line (IC₅₀ 11.0 μM), Carapanolides F (4) showed inhibitory activity in the L1210 cell line (IC₅₀ 15.9 μM), and the cytotoxic activity of Carapanolides I (7) was moderate in all cell lines.     

Bioactive cis-stilbenoids from the tubers of Scirpus yagara

Two new cis-stilbenoids, sciryagarol I (1) and II (2) were isolated from the EtOAc extract of the tubers of Scirpus yagara, together with four known compounds. The structures of all compounds were determined by comprehensive analyses of their spectroscopic data and comparison with literature information. The compounds 3, 4 and 6 were isolated for the first time from this genus. Some compounds were tested for their cytotoxicity against human tumor cell lines and antimicrobial activity. Compounds 1–4 showed significant cytotoxicity against the Hela cell lines with IC₅₀ values ranging from 7.21 to 61.21 μM. 1 and 2 exhibited some antimicrobial activity against Staphylococcus aureus and Candida albicans with uniform MICs of 79.3 μl/ml for 2, and 152 μl/ml for 1, respectively.     

Desmodeleganine,a new alkaloid from the leaves of Desmodium elegans as a potential monoamine oxidase inhibitor

Desmodeleganine (1), a new potential monoamine oxidase inhibitor, along with three known alkaloids, bufotenin (2), hydroxy-N, N-dimethyltryptamine N¹²-oxide (3), 2-(5-methoxy-1H-indol-3-yl)-N, and N-dimethylethylamine (4) were isolated from the leaves of Desmodium elegans. Their structures were elucidated by IR, MS, 1D and 2D NMR spectra. 1 showed strong monoamine oxidase inhibitory activity with IC₅₀ value of 13.92 ± 1.5 μM, when the IC₅₀ value of iproniazid as a standard was 6.5 ± 0.5 μM. The molecular modeling was also performed to explore the binding mode of compounds 1, 2 at the active site of MAO-A and MAO-B.     

New α-glucosidase inhibitors with p-terphenyl skeleton from the mushroom Hydnellum concrescens

The purpose of this study is to elucidate the bioactive components responsible for the the α-glucosidase inhibitory activity detected in the EtOAc extract of the mushroom Hydnellum concrescens. Two new p-terphenyl derivatives, concrescenins A (1) and B (2), in along with six known compounds thelephantins L (3), I (4), J (5), K (6), dihydroauran-tiacin dibenzoate (7), and curtisian A (8) were isolated from the fruiting bodies of H. concrescens. Their chemical structures were elucidated by NMR experiments. Compounds 1–4 and 6–8 showed the inhibitory activity against α-glucosidase with the IC₅₀ of 0.99, 3.11, 4.53, 18.77, 2.98, 5.16, and 8.34 μM, respectively. Kinetic analysis of α-glucosidase indicated that compounds 1 and 2 inhibited the activity of α-glucosidase in a noncompetitive fashion with a Ki value of 0.02 and 0.21 μM, respectively. In antioxidant evaluation, compounds 1 and 4 showed weak DPPH scavenging activity (EC₅₀ = 82.50 and 161.75 μM) and weak reducing ability (EC₅₀ = 193.57 and 152.94 μM). The current research supports the potential use of mushroom-derived p-terphenyl derivatives for the treatment of diabetes.     

Cycloartane Triterpenes from Beesia calthaefolia (Maxim.)

Three new cycloartane triterpenoids (1–3) and two known compounds (4, 5) were isolated from the whole plant of Beesia calthaefolia. Their structures were elucidated by 1D and 2D NMR, HRESIMS and optical rotation spectral data. All isolates were investigated for their inhibitory effects on the classical pathway of the complement system. Among them, compound 4 showed stronger inhibitory activity (IC₅₀ 136.7 μM) than positive control (Rosmarinic acid, IC₅₀ 181.8 μM) while compounds 2 and 3 were moderately active with IC₅₀ value of 206 μM and 200.9 μM. Chemical compound studied in this article: Rosmarinic acid (PubChem CID: 5281792).     

Isocoumarins from American cockroach (Periplaneta americana) and their cytotoxic activities

Four new isocoumarins (1–4), along with three known ones (5–7), were isolated from the 70% ethanol extract of the whole body of the traditional Chinese insect medicine, American cockroach (Periplaneta americana). The structures with absolute configurations of new compounds were elucidated by extensive spectroscopic methods in combination with X-ray diffraction experiment and CD analyses. Compounds 3–5 showed significant cytotoxic activities in HepG2 and MCF-7 cells with IC₅₀ values in the ranges 6.41–23.91 μM and 6.67–39.07 μM, respectively.     

Degraded limonoids and quinoline alkaloids from Dictamnus angustifolius G. Don ex Sweet. and their anti-platelet aggregation activity

A new degraded limonoid, named isodictamdiol A (1), two known degraded limonoids (2, 3) and a new nature product of quinoline alkaloid (4) along with five known quinoline alkaloids (5–9) were isolated from the root bark of Dictamnus angustifolius G. Don ex Sweet.. Certain useful NMR data were generalized to determine the structures of compounds 1 and 4. The structural elucidation of Compound 4 was first reported herein. Compounds 1–9 showed significant inhibitory effects on platelet aggregation induced by ADP at 250 μM, while Compound 4 showed potent anti-platelet aggregation activity.     

Anti-neuroinflammatory constituents from Asparagus cochinchinensis

Three new pregnane glycosides, aspacochinosides N (1), O (2), and P (3) were isolated from the roots of Asparagus cochinchinensis, together with four known furostanol glycosides. Their structures were determined by chemical methods and NMR spectral analysis, including extensive 1D and 2D NMR experiments. Compounds 1–7 were evaluated for their anti-neuroinflammatory activity in LPS-induced BV-2 microglial cells. Compounds 2, 3, and 4 showed significant inhibition on NO production in LPS-induced BV-2 microglial cells with IC₅₀ values of 13.51, 4.72, and 63.57 μM, respectively.     

Cyclodepsipeptides from the ascocarps and insect-body portions of fungus Cordyceps cicadae

A new cyclodepsipeptide cordycecin A (1), together with four known ones beauvericin E (2), beauvericin J (3), beauvericin (4), and beauvericin A (5) was isolated from the ascocarps and insect-body portions of fungus Cordyceps cicadae. Their structures were identified by NMR and MS analyses. The absolute configuration of 1 was confirmed by crystal X-ray diffraction. Compounds 2–5 exhibited a significant inhibitory effect on HepG2 and HepG2/ADM cells with IC₅₀ values ranging from 2.40 ± 0.37 to 14.48 ± 1.68 μM. Interestingly, compounds 3–5 showed cytotoxic activity against multiple drug resistant HepG2 cell line (HepG2/ADM) with IC₅₀ value 25-fold more sensitive to doxorubicin.     

A potent acetylcholinesterase inhibitor from Pancratium illyricum L.

Plants belonging to the Amaryllidaceae contain an exclusive group of alkaloids, known as sources of important biological activities. In the present work, Pancratium illyricum L., a species belonging to this family and endemic of Sardinia (Italy), was investigated for its alkaloid content. Fresh bulbs and leaves were processed separately. Standard extraction and purification procedures were applied to obtain fractions and compounds for GC–MS and NMR analysis. In addition to eight already known alkaloids (1–8), 11α-hydroxy-O-methylleucotamine (9) was isolated for the first time and its structure completely determined by one and two-dimensional ¹H and ¹³C NMR spectroscopy. This new galanthamine-type compound exhibited a pronounced in vitro acetylcholinesterase (AChE) inhibitory activity (IC₅₀ = 3.5 ± 1.1 μM) in comparison to the reference standard galanthamine hydrobromide (IC₅₀ = 1.5 ± 0.2 μM).     

Chemical constituents of Lobelia chinensis

Three new 2, 6-disubstituted piperidine alkaloids (1–3), one new polyacetylene (8), together with eight known compounds (4–7, 9–12) were isolated from the whole plants of Lobelia chinensis. Their structures were elucidated on the basis of spectroscopic data interpretation. The absolute configuration of 1 was established by a convenient Mosher ester procedure in which the sample was treated with MTPA chlorides in deuterated pyridine directly in NMR tube. Cytotoxicities of compounds 1–12 were tested against two human lung cancer cell lines, NCI-H292 and MSTO-211H. Compounds 8 and 9 exhibited moderate cytotoxic activity against the two cancer cell lines with the IC₅₀ values in the range of 9.31–12.36 μM.     

Cleistanthane diterpenes from the seed of Caesalpinia sappan and their antiausterity activity against PANC-1 human pancreatic cancer cell line

Three new cleistanthane diterpenes named tomocinon (1), tomocinol A (2), and tomocinol B (3), were isolated from the EtOAc extract of the seed of Caesalpinia sappan. Their structures were determined by extensive NMR spectroscopic analysis. The absolute stereochemistry of tomocinon (1) has been established by CD spectroscopic analysis. Cleistanthane diterpenes (1–3) represents the novel class of antiausterity agents having preferential cytotoxicity against PANC-1 human pancreatic cancer cell line under nutrient deprived condition with PC₅₀ value of 34.7 μM, 42.4 μM and 39.4 μM, respectively.     

Bioactive polyketides and alkaloids from Penicillium citrinum,a fungal endophyte isolated from Ocimum tenuiflorum

Chemical investigation of the endophytic fungus Penicillium citrinum cultured on white beans or on rice led to the isolation of two new alkaloids (1 and 2), along with fourteen known polyketides (6–12, 14–20) and four known alkaloids (3–5, and 13). The structures of the isolated compounds were determined by extensive analysis of the 1D, 2D NMR, and MS data, and by comparison with the literature. Compound 13, which had been previously obtained only by chemical synthesis, was isolated as a natural product for the first time, while compound 6 was firstly reported as a fungal metabolite. A re-isolation of sclerotinin A (14) revealed it to be a diastereoisomeric mixture (14a and 14b), whose stereochemistry was proposed for the first time based on ROESY experiment. All isolated compounds were evaluated for their cytotoxic and antibacterial activities. Compounds 12 and 17 showed significant cytotoxicity against the murine lymphoma cell line L5178Y with IC₅₀ values of 1.0, and 0.78 μg/ml, respectively, while compounds 5, 11, and 15 were moderately active against Staphylococcus aureus ATCC 29213 (MIC 64 μg/ml).     

Quinolone alkaloids with antibacterial and cytotoxic activities from the fruits of Evodia rutaecarpa

Five new quinolone alkaloids, euocarpines A–E (16–20), four new natural products (1, 4, 12, and 14), and eleven known natural products were isolated from the fruits of Evodia rutaecarpa (Juss.) Benth. The structures of the new compounds were elucidated based on spectroscopic evidence. All compounds were evaluated for their antibacterial activity against three strains and for their cytotoxic activity against four human tumor cell lines. The results revealed that 5, 7–11, 13, 14, and 16–20 exhibited moderate antibacterial activities (MIC values: 4–128 μg/mL), and 9, 11, 14, and 17 exhibited moderate cytotoxic activities against HepG-2, Hela, BEL7402, and BEL7403 (IC₅₀ values: 15.85–56.36 μM).     

Chemical constituents of Swertia yunnanensis and their anti-hepatitis B virus activity

Four new triterpenoids, sweriyunnangenin A (1), sweriyunnanosides A (2), B (3) and C (4), along with nineteen known compounds (5–23) were isolated from Swertia yunnanensis. Based on extensive spectroscopic analyses (1D- and 2D-NMR, HRESIMS, UV, IR, [α]_D), the structures of sweriyunnangenin A (1), sweriyunnanosides A (2), B (3) and C (4) were elucidated as taraxer-14-ene-3α,6β-diol, oleanolic acid 28-O-β-d-glucopyranosyl-(1 → 2)-O-β-d-glucopyranoside, 2α,3β-di-hydroxyolean-12-en-28-oic acid 28-O-β-d-glucopyranosyl(1 → 6)-β-d-glucopyranosyl (1 → 6)-β-d-glucopyranosyl(1 → 2)-β-d-glucopyranoside and hederagenin 28-O-β-d-glucopyranosyl(1 → 6)-β-d-glucopyranosyl(1 → 6)-β-d-glucopyranosyl(1 → 2)-β-d-glucopyranoside, respectively. Twenty-two compounds were evaluated for their anti-HBV activities on the HepG 2.2.15 cell line in vitro, of which nine compounds showed potent anti-HBV activities. Compounds 1, 5–6, 14–16 and 19 showed activities against the secretion of HBsAg (IC₅₀ values from 0.10 to 1.76 mM) and HBeAg (IC₅₀ values from 0.04 to 1.41 mM), and compounds 11 and 13–16 exhibited significant inhibition on HBV DNA replication (IC₅₀ values from 0.01 to 0.09 mM).     

Polyacetylenes and anti-hepatitis B virus active constituents from Artemisia capillaris

Three new polyacetylenes, 8-(Z)-decene-4, 6-diyne-1, 3, 10-triol (1), 1, 3S, 8S-trihydroxydec-9-en-4, 6-yne (2), 3S, 8S-dihydroxydec-9-en-4, 6-yne 1-O-β -D-glucopyranoside (3), and one new glucosyl caffeoate, 1-O-ethyl-6-O-caffeoyl-β -D-glucopyranose (4), together with 34 known compounds were isolated from Artemisia capillaris. The structures of the new compounds were determined by extensive spectroscopic analyses including 1D and 2D NMR, HRESIMS, [α]_D and CD experiments. Among them, 19 compounds showed activity inhibiting HBsAg secretion; 20 compounds showed activity inhibiting HBeAg secretion; and 25 compounds possessed inhibitory activity against HBV DNA replication according to our anti-HBV assay on HepG 2.2.15 cell line in vitro. The most active compound 12 could inhibit not only the secretions of HBsAg and HBeAg, but also HBV DNA replication with IC₅₀ values of 15.02 μM (SI = 111.3), 9.00 μM (SI = 185.9) and 12.01 μM (SI = 139.2).     

Biotransformation on the flavonolignan constituents of Silybi Fructus by an intestinal bacterial strain Eubacterium limosum ZL-II

Eubacterium limosum ZL-II is an anaerobic bacterium with demethylated activity, which was isolated from human intestinal bacteria in our previous work. In this study, the flavonolignan constituents of Silybi Fructus were biotransformed by E. limosum¹ ZL-II, producing four new transformation products — demethylisosilybin B (T1), demethylisosilybin A (T2), demethylsilybin B (T3) and demethylsilybin A (T4), among which T1 and T2 were new compounds. Their chemical structures were identified by ESI-TOF/MS, ¹H NMR, ¹³C NMR, HMBC and CD spectroscopic data. The bioassay results showed that the transformation products T1–T4 exhibited significant inhibitory activities on Alzheimer's amyloid-β 42 (Aβ₄₂²) aggregation with IC₅₀ values at 7.49 μM–10.46 μM, which were comparable with that of the positive control (epigallocatechin gallate, EGCG³, at 9.01 μM) and much lower than those of their parent compounds (at not less than 145.10 μM). The method of biotransformation by E. limosum ZL-II explored a way to develop the new and active lead compounds in Alzheimer's disease from Silybi Fructus. However, the transformation products T1–T4 exhibited decreased inhibitory activities against human tumor cell lines comparing with their parent compounds.     

Sesquiterpene coumarin and sesquiterpene chromone derivatives from Ferula ferulaeoides (Steud.) Korov.

Five novel compounds — three sesquiterpene coumarin derivatives, ferulin A (1), B (2), and C (3), and two sesquiterpene chromone derivatives, ferulin D (4) and E (5), together with eleven known compounds (6–16) have been isolated from the roots of Ferula ferulaeoides (Steud.) Korov. Their structures were established by comprehensive spectroscopic analysis. The biosynthetic pathways leading to these compounds were proposed. The cytotoxicity of all these isolates against HepG2, MCF-7, and C6 cancer cell lines was evaluated and compound 7 displayed the highest potency against HepG2, MCF-7, and C6 with IC₅₀ values 39.9 μM, 37.7 μM, and 16.0 μM, respectively.     

Monoterpene pyridine alkaloids and phenolics from Scrophularia ningpoensis and their cardioprotective effect

Scrophularianines A–C (1–3), three new unusual monoterpene pyridine alkaloids with cyclopenta [c] pyridine skeleton reported from the genus Scrophularia for the first time, together with 15 known compounds (4–18), were isolated from the extract of Scrophularia ningpoensis. Their structures were elucidated on the basis of extensive analyses of spectroscopic evidences. The biogenetic relationship between monoterpene pyridine alkaloids and iridoids was proposed preliminarily. The myocardial protective bioassay indicated that compounds 13 and 14 with a concentration of 10^− 4 M exhibited significantly protective effect against H₂O₂-induced apoptosis in cardiomyocytes.