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A pair of new lignans [(+)- 1 and (-)- 1] and three new compounds (2-4), together with a known compound 5, were isolated from the fruits of Xanthium italicum Moretti. The structures of these compounds were determined on the basis of spectroscopic analysis, particularly HR-ESI-MS and 1 D and 2 D NMR. Compounds 2 and 3 showed antinociceptive effects in an acetic acid-induced writhing test in mice with the writhe inhibition rates of 80.50% and 67.89% at the dose of 20 mg/kg, respectively.

A pair of novel trimeric indole alkaloid enantiomers [(±)

Illihenin A (1), a novel sesquiterpenoid, was isolated from the roots of Illicium henryi. The structure was determined by spectroscopic analyses, ECD calculation, and single-crystal X-ray diffraction. Compound 1 represents a class of novel 5/7/6 tricyclic sesquiterpenoids featuring a rare cage-like tricyclo[6.2.2.01,5]dodecane core. A plausible biosynthetic pathway of 1 by rearrangement of allo-cedrane is proposed. Additionally, 1 showed potent antiviral activity against coxsackievirus B3 with an IC50 value of 2.87 μM.

Xanthanoltrimer A–C (1–3), three xanthanolide sesquiterpene trimers, were first isolated from the fruits of Xanthium italicum Moretti by high-performance liquid chromatography-mass spectrometry-solid phase extraction-nuclear magnetic resonance spectroscopy (HPLC-MS-SPE-NMR). The structures of 1–3 were characterized by a series of spectroscopic methods, NMR calculations and electronic circular dichroism (ECD). Moreover, the cytotoxic, antiviral, anti-inflammatory, and antioxidant activities of 1–3 were screened, but they did not show significant biological activity.

Seven undescribed monoterpenoid indole alkaloids, two N(4)-chloromethylation artifacts, and 10 known alkaloids were isolated from the stems and twigs of Strychnos cathayensis. The corresponding structures were elucidated via spectroscopic data interpretation and electronic circular dichroism. The absolute configuration of (17S)-12-hydroxy-11-methoxydiaboline, the major anomer of 12-hydroxy-11-methoxydiaboline, was characterized by X-ray diffraction analysis for the first time. At an intraperitoneal dose of 30 mg/kg, 12-hydroxy-11-methoxy-N(4)-chloromethyldiaboline and (-)-macusine A exhibited potential analgesic effects with prolongation rates of 99% and 47% for the latency time of hind-paw licking, respectively, compared to the blank control. 12-Hydroxy-11-methoxydiaboline, 12-hydroxy-11-methoxydiaboline N(4)-oxide, retuline N-oxide, and (-)-vincosamide exhibited antiviral activity against Coxsackie virus B3 (CVB3) with IC

Two new hydroxylated ethacrylic acid derivatives (compounds 1 and 2) and 11 new hydroxylated tiglic acid derivatives (compounds 3–13), together with one known compound (compound 14), were isolated ...

Twelve new grayanoids (1−12) along with five known compounds were isolated from flowers of Rhododendron molle. Their structures were fully characterized using a combination of spectroscopic analyses, computational calculations, and single crystal X-ray diffraction. Rhomollone A (1) possesses an unprecedented 5/6/6/5 tetra-cyclic ring system (B-nor grayanane) incorporating a cyclopentene-1,3-dione scaffold. Rhodomollein XLIII (2) is a dimeric grayanoid, containing a novel 14-membered heterocyclic ring with a C2 symmetry axis. The antinociceptive activities of compounds 3, 4, 6, 7, and 12−17 were evaluated by an acetic acid-induced writhing test. Among them, compounds 3, 7, 12, 15 and 16 displayed significant antinociceptive activities at a dose of 20 mg/kg with inhibition rates ranging from 41.9% to 91.6%. Compounds 6 and 13 inhibited 46.0% and 39.4% of the acetic acid-induced writhes at a dose of 2 mg/kg, while compound 17 inhibited 34.3% of the writhes at a dose of 0.4 mg/kg., Graphical abstract Twelve new grayanane-derived diterpenoids including one possesses an unprecedented 5/6/6/5 tetra-cyclic ring system incorporating a cyclopentene-1,3-dione scaffold were isolated from flowers of Rhododendron molle. Some compounds displayed significant antinociceptive activity.Image 1

Three new alkaloids (1-3) were isolated from the rhizomes of Menispermum dauricum. The structures and configurations were established by extensive spectroscopic analyses, including 1D, 2D NMR, and ECD.

Burchellin and its analogues are a class of neolignan natural products containing a rare core with three contiguous stereogenic centers. In previous reports, racemic burchellin was synthesized without accessing each of the enantiomers. In this paper, a concise and efficient total synthetic route to divergently access the enantiomers of burchellin and those of its 1'-epi-diastereoisomer over six steps for each is disclosed, where each of the enantiomers was obtained by preparative chiral phase HPLC purification. The key steps include the construction of a 2,3-dihydrobenzofuran moiety by two Claisen rearrangements and a one-step rearrangement/cyclization and subsequent tandem ester hydrolysis/oxy-Cope rearrangement/methylation to furnish the basic skeleton of burchellin. The structures and absolute configurations of the four stereoisomers were determined using spectroscopic data analyses and comparison of experimental and calculated electronic circular dichroism data. These stereoisomers were found to have potent antiviral effects against coxsackie virus B3, and is the first time that bioactivity has been reported for these compounds.

Four minor undescribed terpenoids, including a monoterpenoid (1) and three triterpenoids (3, 6 and 7), together with 26 known terpenoids were isolated from the stems and twigs of Rhododendron Ovatum. Their structures were identified by extensive spectroscopic analyses and electronic circular dichroism (ECD) techniques. Compound 10 showed excellent cytotoxicity against human colon cancer cell (HCT-116) with IC50 value of 2.56 μM. Compounds 9 and 19 exhibited partly inhibitory effects on nitric oxide production stimulated by lipopolysaccharide-induced neuroinflammation in microglia cells at 10 μM with inhibition ratios of 39.70% and 28.08%, respectively.

A pair of novel trimeric indole alkaloid enantiomers [(±)-8], five new bisindole alkaloids [4–7 and (±)-9], and three pairs of new monomeric indole alkaloid enantiomers [(±)-1–(±)-3], together with seven known alkaloids (10–16), were isolated from the bark of Acacia confusa. Their structures were determined on the basis of spectroscopic methods, especially by NMR data analyses combined with single-crystal X-ray diffraction and electronic circular dichroism analyses. Compounds 4 and 11–16 exhibited significant antinociceptive activities in an acetic acid-induced writhing test. Compounds (+)-9 and (−)-9 displayed anti-inflammatory activities through the inhibition of the NF-κB pathway, with inhibitory rates of 68.9% and 59.5%, respectively, at a concentration of 10 µM.

Chemical investigation of an alcohol extract from the twigs and leaves of Illicium henryi Diels resulted in the isolation of two new acorane-related seco-sesquiterpenes (1 and 3), two new acorane-related seco-norsesquiterpenes (2 and 4), one new 2-epi-cedrane sesquiterpene (5), eight new acorane-type sesquiterpenes (6-13), and a known major constituent of acorenone B (14). Their structures were established by interpreting extensive spectroscopic data, including HRESIMS, NMR (

Three seco-prezizaane-type sesquiterpene lactones, one phenylpropanoid, and two lignans were isolated from the 95% ethanol extract of stems and branches of Illicium ternstroemioides with silica gel column chromatography, ODS column chromatography, and preparative HPLC. Based on the spectral data, they were identified as burmanicumolide D(1), veranisatin A(2), veranisatin B(3), dihydroconiferylalcohol(4), pinoresinol(5),(-)-matairesinol(6), respectively. Among them, compound 1 was a new seco-prezizaane-type sesquiterpene lactone, and 2-6 were obtained from this plant for the first time. None of these compounds display antiviral or cytotoxic activities.

One undescribed diterpenoid illisimonone A, four undescribed sesquiterpenes named (±)-simonones A, simonterpenoids A and B, and two undescribed lignans, illisimonins A and B, along with five known compounds were isolated from the fruits of Illicium simonsii. Their structures were elucidated by extensive spectroscopic data. The absolute configuration of illisimonone A was determined by single-crystal X-ray diffraction analysis. Illisimonone A showed potential antiviral activity against the Coxsackie B3 virus, with an IC

A pair of new lignans [(+)

Twenty-one new triterpenoids (1–21) and fifteen known triterpenoids (22–36) were rapidly isolated from Rhododendron latoucheae by the hyphenated technique HPLC‒MS‒SPE‒NMR. The structures of 1−21 were elucidated from NMR, MS, and extensive spectroscopic methods and electronic circular dichroism (ECD) analyses. Notably, compound 1 is the first example of 23-norquinone methide. Compounds 1, 2, 6, 14, 21, 28, 30, and 35 exhibited potent activities against HSV-1, with IC50 values from 0.71 to 14.62 μM.

Thirteen compounds were isolated from the lipid-soluble extracts of Illicium ternstroemioides A. C. Smith, including eleven previously undescribed prenylated C

The construction of libraries of stereoisomers of natural products serves as an important approach to investigating the correlation between the stereostructure and biological activity. However, the total synthesis and isomerzation of polycyclic scaffolds with multiple chrial centers are rare. Spirooliganin (1), a new skeleton natural product isolated from the plant Illicium oligandrum, was structurally characterized by comprehensive analysis of NMR spectroscopic data and ECD which revealed an unprecedented 5–6–6–6–7 polycyclic framework with six chiral centers. Here we report a 17-step total synthesis to prepare a library of stereochemically diverse isomers of spirooliganin, including 16 diastereoisomers and 16 regioisomers. In addition to a regioselective hetero-Diels–Alder cycloaddition, the synthetic strategy involves a photo-induced stereoselective Diels–Alder reaction, which gives only the abnormal trans-fused product as rationalized by density functional theory calculations. Preliminary biological evaluation showed that spirooliganin and regioisomers 39 exhibited potent inhibition of Coxsackievirus B3. It also revealed the pharmacophore effect of the D-ring (16R,18R,24R, and 26R) for their antiviral activities., Library construction of stereochemically diverse isomers to investigate the relationship between stereoconfiguration and anti-coxsackie virus B3 activity.

Thirty new pentacyclic triterpenoids, including five oleanane-type (1–5), twenty-three ursane-type (9–23, 26–33) and two taraxerane-type (24 and 25), along with fourteen known triterpenoids, were isolated from the stems and branches of Enkianthus chinensis. Their structures were elucidated by extensive spectroscopic analyses, X-ray crystallographic data and electronic circular dichroism (ECD) techniques. Sixteen compounds (1–5, 9–13, 20, 22, 32, 34–36) bearing a gem-hydroxymethyl group at C-4 represent rare examples of pentacyclic triterpenoids. In the in vitro biological activity evaluation, compounds 8, 9, 12–14, 17, 24, and 44 exhibited potent hepatoprotective effects at 10 μM. Moreover, compound 25 showed latent activity against HSV-1 with an IC50 value of 6.4 μM.

Illihenin A (

Two new hydroxylated ethacrylic acid derivatives (compounds

Seventeen new prenylated C

Three new alkaloids (

Ten seco-prezizaane sesquiterpenes were isolated from the water-soluble fraction of the fruit of Illicium lanceolatum using the combined methods of silica gel column chromatography,Sephadex LH-20 column chromatography,and RP-preparative HPLC. They were elucidated as majusanol E( 1),2α-hydroxycycloparviflorolide( 2),2β-hydroxy-3,6-dedioxypseudoanisatin( 3),majusanol A( 4),merrillianone( 5),cycloparvifloralone( 6),3α-hydroxycycloparvifloralone( 7),1,2-dehydrocycloparvifloralone( 8),henrylactone C( 9),and( 11) 7,14-ortholactone-3α-hydroxyfloridanolide( 10) according to the NMR data. All compounds were obtained from this plant for the first time. Neuroprotection activity,anti-Coxsackie B3 virus,and anti-H3 N2 virus experiments were carried out to test their bioactivities. The bioassay results showed that compounds 1,4,6,7,9 and 10 displayed weak protective effects of the damage of nerve SH-SY5 Y cell induced by monosodium glutamate.

Detailed phytochemical investigation of the roots of Erythrophleum fordii furnished seven undescribed cassane-type diterpenoids, erythrocassanoids A-E and erythro-norcassanoids A, B and two known clerodane diterpenes, 15-hydroxy-3-cleroden-2-one and methyl ester of 2-oxopopulifolic acid. Their structures were determined by 1D, 2D NMR and HRESIMS analysis. The antiviral activities of these compounds were evaluated. Among them, 15-hydroxy-3-cleroden-2-one and methyl ester of 2-oxopopulifolic acid showed antiviral activities against influenza virus and coxsackie virus with IC50 values ranging from 11.11 to 29.60 μM.

One new sesquiterpene lactone, corialactone E ( 1 ), one new neolignan, coriarianeolignan A ( 2 ), together with three known apocarotenoids ( 3-5 ) and one known neolignan ( 6 ) have been isolated from a CHCl 3 extract of the roots of Coriaria nepalensis . The structures including absolute configurations of 1-6 were elucidated through extensive NMR, HR-ESIMS, and CD data analysis. Structurally, compound 1 possessed novel variations in the structure, including the newly formed ether ring of C-3/O/C-9 and the lactone ring connecting C-13 and C-5. Compound 5 showed cytotoxic activity against SKOV3 (human ovarian cancer) cells with IC 50 values of 4.67 μmol/L. In vivo system, compound 3 showed anti-convulsant activity by 34% at the dose of 5 mg/kg.

Rhododendron molle G. Don is one of the most potent traditional Chinese medicines for pain relief. Prior investigations have shown that Rhododendrons are rich sources of terpenoids. In our continuing efforts to identify structurally unique and biologically interesting diterpenoids, the fruits of R. molle were collected from Guangxi Province. A chemical study was carried out on the EtOH extract, which led to the isolation of 18 diterpenoids including 12 new compounds. The isolation and structural elucidation of new compounds 1 – 12 , as well as the evaluation of the antinociceptive activities of these compounds were reported.

During our continuing study on the roots of Pieris formosa, twelve new grayanane diterpenoids (1–12), together with eight known compounds (13–20), were obtained. Their structures with absolute configurations were characterized by a series of spectroscopic methods and X-ray diffraction. Compounds 1, 2, 4–5, 7–8, 14, and 19 exhibited significant analgesic activity in an acetic acid-induced writhing test. In particular, 7 and 14 were found to be 5 times more potent than morphine in the acetic acid-induced writhing test model. Compounds 1, 4, 9, 13, and 18 showed antifeedant activity against Plutella xylostella at 0.5 mg/mL. Compound 4 exhibited a 38.3% inhibitory effect against the KCNQ2 potassium channel at a concentration of 10 μM.

Thirteen compounds were isolated from the lipid-soluble extracts of Illicium ternstroemioides A. C. Smith, including eleven previously undescribed prenylated C6–C3 compounds, a previously undescribed prenylated C6–C3 derivative-abscisic acid ester hybrid, and a known compound (4S)-illicinone I. Their structures and configurations were mainly elucidated by spectroscopic analyses, CD experiments and X-ray crystallography. (2S,4R,11S)-4-O-methyl-12-chloroillifunone C, (2S,4R,11R)-2,3-dihydro-4-O-methyl illioliganfunone D, and illiternfunol A were found to exhibit weak activity against Coxsackievirus B3, with IC50 values ranging from 27.8 to 33.3 μM. Illiternone B exhibited more potent activities against Coxsackievirus B3 and influenza virus A than did its geometric isomer illiternone A, with IC50 values of 7.7 μM and 2.5 μM, respectively. None of these compounds displayed cytotoxic activities.

Eight undescribed humulane-type sesquiterpenoids (xanthspinol A-E, I, J and N), three undescribed germacrane-type sesquiterpenoids (xanthspinol F, G and O) and twelve known compounds were isolated from the fruits of Xanthium spinosum. The structures of the undescribed compounds were elucidated by analyses of spectroscopic data, electronic circular dichroism (ECD) calculations, dimolybdenum tetraacetate [Mo2(OAc)4]-induced circular dichroism (ICD) spectra, a CD exciton chirality method and the modified Mosher's method. Xanthspinol A and B featured a humulane skeleton containing a 2,5-dihydrofuran fragment. Putative biosynthetic pathways for the undescribed compounds are proposed. Xanthspinol N, 8-epi-isoxanthanol and deacetyl-4-epixanthanol showed moderate activity against Coxsackie virus B3 (CVB3) with IC50 values of 8.70, 3.70 and 3.70 μM, respectively.

As a traditional Chinese medicine, Patrinia scabiosifolia Link has been used to treat various inflammatory-related diseases, and recent studies have shown that it possesses potent anti-inflammatory activity. Therefore, phytochemical investigation on whole plants of P. scabiosifolia were carried out, which led to the isolation of two new iridoid glucosides, patriniscabiosides A (1) and B (2), together with six known compounds (3–8). The structural elucidation of all compounds was performed by HRESIMS and extensive spectroscopic analyses including IR, 1D, 2D NMR, and electronic circular dichroism (ECD). All the isolated compounds were tested for their anti-inflammatory activity using the NF-κB-Dependent Reporter Gene Expression Assay, and compound 3 displayed anti-inflammatory activity through the inhibition of the NF-κB pathway, with an inhibitory rate of 73.44% at a concentration of 10 μM.

Illisimonin A, an unprecedented sesquiterpenoid with a tricyclo[5.2.1.01,6]decane skeleton, was isolated from the fruits of Illicium simonsii. The structure and absolute configuration of 1 were determined using extensive spectroscopic evidence and electronic circular dichroism (ECD) calculations. It was determined that 1 possesses a caged 2-oxatricyclo[3,3,0,14,7]nonane ring system fused to a five-membered carbocyclic ring and a five-membered lactone ring. A plausible biogenetic pathway for 1 was proposed, and 1 showed neuroprotective effects against oxygen-glucose deprivation (OGD)-induced cell injury in SH-SY5Y cells with an EC50 value of 27.72 μM.

Eight new isopimarane diterpene glucosides (1–8) and one new nor-diterpene glucoside (9) were isolated from the twigs and leaves of Lyonia ovalifolia. The structures of the new compounds (1–9) were determined based on extensive spectroscopic analysis, including HRESIMS, and 1D and 2D NMR data. The absolute configuration of compounds 1a (the aglycone of 1) and 6a (the aglycone of 6) were established using X-ray crystallography, those of compounds 2, 4, and 5 were established by ECD experiments, and that of compound 9 was established using a modified Mosher method. These isopimarane diterpenes are the first isolated from the Ericaceae family. Compound 9 is the first diterpene glucoside found in nature with the novel 14,15-dinor-9,10-seco-labdane skeleton. Anti-bacterial testing showed that compounds 3–7 have inhibitory effects against different strains at the concentration of 10−4 moL/L.

Seven pairs of sesquiterpenes (1a/1b–7a/7b), a new peroxy-bridge sesquiterpene (8), and a new peroxy-bridge norsesquiterpene (9), together with five known compounds, were isolated from the roots of Artabotrys hexapetalus. Their structures with absolute configurations were elucidated based on extensive spectroscopic analysis, especially the modified Mosher's method, and electronic circular dichroism (ECD) analyses. Notably, the resolutions of seven pairs of stereoisomers (1a/1b–7a/7b) were achieved by chiral HPLC. All the compounds were evaluated for their antiviral and cytotoxic activities. Compounds 1a, 1b, 12a–12d, and 14 showed moderate antiviral activity against Coxsackie virus B3 with IC50 values of 6.41–33.33 μM and SI values > 2.1, whereas compounds 5b, 8, and 12a exhibited weak activity against influenza virus A H3N2 with IC50 values ranging from 19.24 to 33.33 μM and SI values > 3.0. Compound 12c exhibited selective cytotoxicity against A2780 cell line with an IC50 value of 8.30 μM, while compound 12d showed potent cytotoxicity against HCT-116, HepG2, and A2780 cell lines with IC50 values of 3.24, 3.23, and 3.14 μM, respectively.

Three new phenolics ( 1 – 3 ) and twenty-eight known compounds ( 4 – 31 ) were isolated from an ethanolic extract of roots of Alangium chinense . Compound 11 exhibited antiviral activity against Coxsackie virus B3 with IC 50 values of 16.89 μmol/L. Compounds 1 , 10 – 17 , 19 – 21 , and 23 showed strong antioxidant activity against Fe 2+ -cysteine-induced rat liver microsomal lipid peroxidation, with IC 50 values of 0.14–8.18 μmol/L.

Seventeen new 3,4-secograyanoids (1–17), together with seven known compounds (18–24), were isolated from the roots of Pieris formosa. Their structures with absolute configurations were characterized by a series of spectroscopic methods and X-ray diffraction. Compounds 1, 2, 4–8, 10–13, and 16–24 exhibited significant analgesic activity at 5.0 mg kg−1 (ip) compared to vehicle-injected mice (p < 0.05). In particular, compounds 16 and 17 showed highly potent activities with inhibition rates of 63.5% and 69.9%, respectively.

Six new glycosides (1-6), together with three known ones, were isolated from the twigs and leaves of Rhododendron latoucheae. Their structures were elucidated based on the spectroscopic data, including infrared spectrometry, mass spectrometry, and nuclear magnetic resonance experiments, along with Mosher's method. In addition, all compounds were tested their antiviral (herpes simplex virus-1 and influenza A/95-359) activities.

Two new azafluoranthene alkaloids (1 and 2), and a new phytoecdysone (3), were isolated from the stems of Cyclea barbata Miers, together with six known compounds (4-9). Their structures were elucidated by spectroscopic data analysis and comparison with published data. This is the first report of azafluoranthene alkaloids (1 and 2) and phytoecdysones (3, 8, and 9) from Cyclea genus. In in vitro bioassay, four isolates (3, 5, 6, and 9) showed moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells.

The phytochemical study of the ethanol extract of the leaves and twigs of Rhododendron decorum afforded a new ascorbic acid derivative (1), a new ionone analogue (2), a new ursane-type triterpenoid glucoside (3), and four known compounds (4−7). The structures were elucidated by spectroscopic analyses, including HRESIMS, 1D, and 2D NMR. The anti-neuroinflammatory activities of the compounds were evaluated by measuring inhibitory effects of LPS-induced NO production in BV2 cells.

Two new azafluoranthene alkaloids (1 and 2), and a new phytoecdysone (3), were isolated from the stems of Cyclea barbata Miers, together with six known compounds (4–9). Their structures were elucidated by spectroscopic data analysis and comparison with published data. This is the first report of azafluoranthene alkaloids (1 and 2) and phytoecdysones (3, 8, and 9) from Cyclea genus. In in vitro bioassay, four isolates (3, 5, 6, and 9) showed moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells.

Three new megastigmane glucosides (1-3) and two new monoterpenes (4-5), together with 14 related known compounds (6-19) were isolated from the twigs and leaves of Lyonia ovalifolia. The structures of the new compounds were determined by extensive MS, NMR, CD experiments and chemical methods. Compounds 2, 6, and 18 displayed potent antiviral activity against Coxsackie B3, with IC50 values between 6.4 and 14.6 µM. Additionally, compounds 6, 10, and 11 exhibited noteworthy anti-inflammatory activities, with inhibition rates ranging from 54.55% to 83.33% under the concentration of 10-5 M.

Seventeen new prenylated C6-C3 derivatives, namely, illifargeins A–M (1–13), including three pairs of enantiomers (1, 5, and 12) and one norillifargeal A (14), together with eight known analogues (15–22), were isolated from the stems and leaves of Illicium fargesii. The structures of the new compounds were elucidated using spectroscopic data (UV, IR, 1D and 2D NMR, and HRESIMS). Their absolute configurations were determined by using experimental and calculated ECD data analysis, as well as a modified Mosher’s method. Compounds 1a, 1b, 2, 3, 5a, 7, 10, 11, 15, 16, 19, and 20 showed potential activity against Coxsackie virus B3, with IC50 values ranging from 6.23 to 33.33 µM. Compounds 9 and 15 exhibited potential activity against influenza virus A, with IC50 values of 11.11 and 19.24 µM, respectively. Compounds 2, 3, and 18 exhibited potential anti-oxidant activity, with IC50 values ranging from 1.43 to 6.71 µM.

Medulloblastoma (MB) and glioblastoma (GBM) are the most prevalent malignant brain tumors. The identification of novel therapeutic strategies is urgent for MB and GBM patients. Herein, we discovered 13a-(S)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b]-indolizidine (PF403) strongly exhibited inhibitory activity against Hedgehog (Hh) pathway-hyperactivated MB and GBM cells with a 50% inhibitory concentration (IC50) of 0.01 nM. CAT3 was designed and synthesized as the prodrug of PF403 and displayed significant in vivo efficacy against MB and GBM. Mechanistic study revealed that CAT3 inhibited MB and GBM primarily by interrupting the Hh signaling pathway. At the molecular level, PF403 inhibited the cell surface accumulation of the Smoothened (Smo) receptor by directly binding or enhancing the interaction of Smo with the repressor Ptch1. Furthermore, PF403 significantly repressed Gli1 nuclear accumulation and transcription by promoting Sufu-Gli1 and PKA-Gli1 interactions. Collectively, our studies support the hypothesis that CAT3 is a promising therapeutic agent for the treatment of Hh-driven MB and GBM.

Two pairs of oligomeric coumarin enantiomers, spirotriscoumarin A [(+)-1 and (−)-1] and spirotriscoumarin B [(+)-2 and (−)-2], with a spirodienone-sesquiterpene fused skeleton were isolated from Toddalia asiatica. Their structures were unambiguously established using spectroscopic data, X-ray diffraction analysis, and the electronic circular dichroism (ECD) method. The racemic mixtures (±)-1 and (±)-2 exhibit 3-to-6-fold stronger antiviral activity against influenza virus A (H3N2) (IC50: 3.13 and 2.87 μM, respectively) than their corresponding optically pure enantiomers.

Nine new corynanthe-type alkaloids (1–9) and five known analogues (10–14) were isolated from the seeds of Strychnos angustiflora. Their structures were established based on extensive spectroscopic and spectrometric data, and the structure of 1 was confirmed using single-crystal X-ray crystallography. Based on NMR and electronic circular dichroism (ECD) data analyses, the R absolute configuration of the N-4 stereogenic center of 2 was shown to be opposite to that of 1. In addition, the configurations of compounds 4–8 were established by hydrolysis experiments, and the antirhine moieties were determined to be identical to 11, which was confirmed for the first time using single-crystal X-ray crystallography data analysis. Compounds 1, 4, 10, and 11 exhibited analgesic activity, which increased the hind-paw licking latency rates by 56–78% at an intraperitoneal dose of 20 mg kg−1 during a hot-plate test in mice.