Plasiatine, an Unprecedented Indole-Phenylpropanoid Hybrid from Plantago asiatica as a Potent Activator of the Nonreceptor Protein Tyrosine Phosphatase Shp2.

Plasiatine (1), isolated from the seeds of Plantago asiatica, is an unprecedented indole analogue linked to a phenylpropanoid moiety via a carbon bond that builds up a novel heteromeric construction with a C19N2 scaffold. Its structure was determined by spectroscopic data and computational evidence. Notably, experimental assay demonstrated that 1 significantly enhanced the activity of the nonreceptor protein tyrosine phosphatase Shp2 in vitro in a concentration-dependent manner with an EC50 value of 0.97 µM, and activated phosphorylation of ERK, a known target of Shp2. Moreover, plasiatine (1) promoted hepatocellular HepG2 cells migration. Molecular docking suggested that plasiatine (1) binds to the catalytic cleft of Shp2. These results identified plasiatine (1) as the first small molecule Shp2 activator, and it warrants further investigation as a novel pharmaceutical tool to study the function of Shp2 in tumorigenesis.

Antiviral sesquiterpenes from leaves of Nicotiana tabacum.

Three unreported sesquiterpenes possessing two new skeletons, tabasesquiterpenes A-C (1-3), together with three known sesquiterpenes (3-6) were isolated from the leaves of Nicotiana tabacum. Their structures were determined mainly by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. Compounds 1-6 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that compound 2 exhibited high anti-TMV activity with inhibition rate of 35.2%, which were higher than that of positive control (ningnanmycin). The other compounds also showed potential anti-TMV activity with inhibition rates in the range of 20.5-28.6%.

LC-UV-Guided Isolation and Structure Determination of Lancolide E: A Nortriterpenoid with a Tetracyclo[5.4.0.0(2,4).0(3,7)]undecane-Bridged System from a "Talented" Schisandra Plant.

Lancolide E (1) featuring a complex tetracyclo[5.4.0.0(2,4).0(3,7)]undecane-bridged system that is constructed by an eight-, a three-, and two five-membered carbon rings in a sterically congested region was obtained in trace amounts from a "talented" schinortriterpenoid producer Schisandra lancifolia. Its structure was fully characterized by combining 2D NMR spectroscopy, theoretical calculations, and X-ray diffraction analysis. The biogenetic pathway of 1 was proposed to involve a Prins cyclization.

Aspergillines A-E, highly oxygenated hexacyclic indole-tetrahydrofuran-tetramic acid derivatives from Aspergillus versicolor.

Aspergillines A-E (1-5) are highly oxygenated cyclopiazonic acid (CPA)-derived alkaloids bearing a rigid and sterically congested hexacyclic indole-tetrahydrofuran-tetramate scaffold, isolated from the endophytic fungus Aspergillus vesicolor. Apergillines A-C represent a new subclass of CPA-derived alkaloids, and aspergillines B and E possess a butanoic acid methyl ester moiety. The structures, including absolute configuration, were elucidated by interpretation of the NMR, X-ray crystallographic, and circular dichroism data. All compounds displayed anti-TMV and cytotoxic activities.

Biphenyls from Nicotiana tabacum and their anti-tobacco mosaic virus.

Five new biphenyls, tababiphenyls A-E (1-5), together with five known ones (5-10), were isolated from the leaves of Nicotiana tabacum, of which compound 1 possessed a seldom reported 6-carbons unit in biphenyls. Their structures were established on the basis of extensive spectroscopic analyses. All compounds were tested for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that compounds 3 and 5 exhibited high anti-TMV activities with inhibition rate of 48.4% and 32.1%, respectively, which were higher than that of positive control (ningnanmycin). The other compounds also showed potential anti-TMV activities with inhibition rates in the range of 18.6-28.7%, respectively.

Structural characterization and antioxidative activity of lancifonins: unique nortriterpenoids from Schisandra lancifolia.

Six unique nortriterpenoids, lancifonins A-F (1-6), were isolated from Schisandra lancifolia. Their absolute configurations were determined by X-ray diffraction and ECD calculation. The conformational analysis of 1 was performed due to the unanticipated changes of Cotton effects in its ECD spectrum. Compounds 5 and 6 possess a unique 7/7 fused carbocyclic core with an internal ester bridge between C-9 and C-14, and 5 exhibited protective activity against H2O2-induced oxidative damage on Caco-2 cells.

Structure and bioactivity of triterpenoids from the stems of Schisandra sphenanthera.

Two new triterpenoids, schisphendilactone A and B (1 and 2), together with three known triterpenoids, were isolated from the stems of Schisandra sphenanthera. Their structures were elucidated by spectroscopic methods, and the absolute configuration of 1 was determined by single-crystal X-ray diffraction. Compound 2 showed moderate inhibitory activity against SW480 cancer cell line, and compound 5 exhibited promising anti-HIV-1 activity with EC50 value of 0.52 µg ml(-1) and therapeutic index value of 117.12.

Bioactive lignans from the leaves and stems of Schisandra wilsoniana.

Three new dibenzocyclooctadiene lignans, marlignans M-O (1-3), together two known ones, were isolated from the leaves and stems of Schisandra wilsoniana. The structures of 1-3 were elucidated by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. Compound 2 showed anti-HIV-1 activity with an EC50 value of 5.82 microg/mL and a therapeutic index (TI) of more than 12.8. Compound 3 showed obvious bioactivity in inhibiting Epstein-Barr virus early antigen (EBV-EA) activation.

Six new lignans from the leaves and stems of Schisandra sphenanthera.

Six new lignans, schisphenlignans F-K (1-6), together with ten known ones, were isolated from the leaves and stems of Schisandra sphenanthera. Their structures were elucidated on the basis of spectroscopic methods, including extensive NMR, MS and CD spectra. In addition, some compounds were tested for their acute activity on insulin sensitivity in 3T3-L1 differentiated adipocytes and anti-HIV-1 activity.

Phenolic constituents from Parakmeria yunnanensis and their anti-HIV-1 activity.

Three new phenolic compounds, yunnanensins A-C (1-3), together with fourteen known ones (4-17), were isolated from the leaves and stems of Parakmeria yunnanensis. The structures of new compounds were established on the basis of extensive spectroscopic analyses. Several compounds showed weak anti-HIV-1 activity.

Schisphenlignans A-E: five new dibenzocyclooctadiene lignans from Schisandra sphenanthera.

Five new dibenzocyclooctadiene lignans, schisphenlignans A-E (1-5), together with eight known ones, were isolated from the stems of Schisandra sphenanthera. The structures of 1-5 were elucidated based on the analysis of their NMR, MS and circular dichroism (CD) spectra. Some isolates were tested for their acute activities on insulin sensitivity in 3T3-L1 differentiated adipocytes, but none of them showed significant bioactivity with 10 µM administration of the tested compounds.

Bioactive phenolics and terpenoids from Manglietia insignis.

Four new compounds, maninsigins A-D (1-4), including two new neolignans (1-2) and two new sesquiterpenes (3-4), as well as ten known compounds (5-14), were isolated from the leaves and stems of Manglietia insignis. Their structures were established on the basis of extensive spectroscopic analyses. In addition, some compounds were tested for their cytotoxic and neurite outgrowth-promoting activities, as well as their antagonistic activity toward FXR ligand.

Kadcoccitones A and B, two new 6/6/5/5-fused tetracyclic triterpenoids from Kadsura coccinea.

A pair of new triterpenoid epimers, kadcoccitones A (1) and B (2), together with a new biogenetically related compound kadcoccitone C (3), were isolated from Kadsura coccinea. The epimers featured an unprecedented carbon skeleton with a 6/6/5/5-fused tetracyclic ring system unit and a C(9) side chain. Their structures were determined by spectroscopic data, ECD calculation, and single-crystal X-ray diffraction. Compounds 1 and 3 showed anti-HIV-1 activity with an EC(50) value of 47.91 and 32.66 µg/mL, respectively.

Lanostane triterpenoids from the stems of Schisandra glaucescens.

Ten new triterpenoids, schiglausins A-J (1-10), as well as four known compounds, were isolated from the stems of Schisandra glaucescens. Their structures were elucidated on the basis of spectroscopic methods, including extensive NMR spectra and CD experiment. Compound 8 was determined to be a norlanostane triterpenoid. The crystal structure of compound 1 has been determined using single-crystal X-ray analysis while its absolute configuration was assigned on the basis of the CD spectrum. All isolates were tested for their FXR agonistic and antagonistic effects.

New bicyclo[3.1.0]hexane unit ent-kaurane diterpene and its seco-derivative from Isodon eriocalyx var. laxiflora.

Neolaxiflorin A (1), an unprecedented ent-kaurane diterpenoid with a bicyclo[3.1.0]hexane unit, and its seco-derivative, neolaxiflorin B (2), along with two known compounds 3 and 4 were isolated from the leaves of Isodon eriocalyx var. laxiflora. The absolute configuration of 1 was determined by spectral methods and single crystal X-ray diffraction analysis. Compound 4 and the synthesized compound 5 exhibited significant cytotoxicity.

Anti-HIV-1 activity of lignans from the fruits of Schisandra rubriflora.

This study investigated the 70% aqueous acetone extract of the fruits of Schisandra rubriflora which led to the isolation of eight lignans, including a new isolate, rubrisandrin C (1), and seven known lignans (2-8). The structure of 1 was established by extensive 1D and 2D NMR spectroscopy and its absolute stereochemistry was determined by CD spectrum. Compounds 1-5 and 7-8 were evaluated for their anti-HIV-1 activity that showed inhibitory activity on HIV-1(IIIB) induced syncytium formation with EC(50) values in the range of 2.26 approximately 20.4 microg/mL. Compounds 1 and 7 exerted their obvious protection of HIV-1(IIIB) inducted MT-4 host cells lytic effects with a selectivity index of 15.4 and 24.6, respectively.