Bisleuconothine A, a bisindole alkaloid, inhibits colorectal cancer cell in vitro and in vivo targeting Wnt signaling.

Wnt signaling pathway is aberrantly activated in a variety of cancers, especially in colorectal cancer and small molecule antagonists of Wnt/ß-catenin signaling are attractive candidates for developing effective therapeutics. In the present study, we identified Bisleuconothine A, a bisindole alkaloid with an eburnane-aspidosperma type skeleton, as a novel and selective Wnt signaling inhibitor by using a cell-based luciferase assay system. Our study found that Bisleuconothine A down-regulated the endogenous Wnt target gene expression through promoting phosphorylation of ß-catenin and the subsequent inhibition of its nuclear translocation in HCT116 and SW480 colorectal cancer cells. In vitro, Bisleuconothine A inhibited cell proliferation through induction of apoptosis by increasing the cleavage of caspases in HCT116 and SW480 colorectal cancer cells. Moreover, in vivo, Bisleuconothine A dramatically suppressed tumor growth in HCT116 Xenograft. And further analysis showed that Bisleuconothine A suppressed the Wnt target gene expression in HCT116 Xenograft, which was associated with up-regulation of ß-catenin phosphorylation and subsequent Wnt signaling inhibition. Taken together, our study indicated that bisindole alkaloids could be included as a new chemotype of small-molecule Wnt signaling inhibitors, and have great potential to be further developed for anti-tumor agents.

Sesquiterpenoids from Tussilago farfara and their inhibitory effects on nitric oxide production.

Tussilagone (TSL) and its allied sesquiterpenoids were considered as the main active principles of the flower buds of Tussilago farfara, which has been widely used in China as an antitussive herbal medicine. Six new bisabolane-type sesquiterpenoids, tussfararins A-F (1-6), along with 12 known sesquiterpenoids, were isolated from the flower buds of T. farfara. Structures of the new compounds were elucidated by extensive spectroscopic analysis. The biological analysis showed that compounds 1, 3, 6, and 7 inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells with IC50 values of 13.6-24.4 µM.

Syntheses of novel ß-carboline derivatives and the activities against five tumor-cell lines.

A series of ß-carbolines possessing the aryl group at C-1 position has been synthesized from tryptophan. The newly synthesized compounds were screened for their in vitro anticancer activity against various human cancer cell lines by MTT assay. Some of them exhibited anticancer activity with IC50 values lower than 10µM outdistanced the cisplatin level. Structure-activity relationship reveals that the alcohol substituents at C-3 position played an important role in inhibition activity.

Kadcotriones A-C: tricyclic triterpenoids from Kadsura coccinea.

Three new triterpenoids, kadcotriones A-C (1-3), together with the biogenetically related lanostane-type triterpenoid (4), were isolated from Kadsura coccinea. Compound 1 features a 12,14ß-dimethyl 6/6/6-fused tricyclic skeleton, while 2 and 3 are characterized by a 6/6/5-ring system. Their structures were determined by NMR and electronic circular dichroism spectroscopic methods. Compounds 2 and 4 exhibited anti-HIV-1 activities with EC50 values of 30.29 and 54.81 µM, respectively.

Cytotoxic indole alkaloids from Tabernaemontana divaricata.

Five new vobasinyl-ibogan-type bisindole alkaloids, tabernaricatines A-E (1-5), two new monomers, tabernaricatines F and G (6 and 7), and 24 known indole alkaloids were isolated from the aerial parts of Tabernaemontana divaricata. Alkaloids 1 and 2 are the first vobasinyl-ibogan-type alkaloids possessing a six-membered ring via an ether linkage between C-17 and C-21. All compounds except for 3 were evaluated for their cytotoxicity against five human cancer cell lines; conophylline showed significant bioactivity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cells with IC50 values of 0.17, 0.35, 0.21, 1.02, and 1.49 µM, respectively.

Triterpenoids and steroids with cytotoxic activity from Emmenopterys henryi.

Two new ursane-type triterpenoids, 3ß,19α,23-trihydroxyurs-12-en-24-al-28-oic acid (1) and 3ß,19α,24-trihydroxy-23-norurs-12-en-28-oic acid (2), two new pregnane derivatives, 3ß,12ß-dihydroxy-5α-pregnane-14,16-dien-20-one (9) and 12ß-hydroxy-5α-pregnane-14,16-dien-3,20-dione (10), and eight known compounds were isolated from the twigs and leaves of Emmenopterys henryi. The structures of the new compounds were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR experiments. Compounds 4, 11, and 12 showed cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cell lines with IC50 values in the range of 3.11-20.12 µM.

Diterpenoids from the twigs and leaves of Fokienia hodginsii.

Five new isopimarane diterpenoids, fokihodgins A-E (1-5), four new labdane diterpenoids, fokihodgins F-I (6-9), and one new icetexane diterpenoid, fokihodgin J (10), as well as 18 known diterpenoids were isolated from Fokienia hodginsii. The structures of the new compounds were determined on the basis of their spectroscopic analysis, and the absolute configurations of 1 and 6 were established by X-ray crystallographic analysis. Compound 9 showed moderate cytotoxicity against HL-60 and SMMC-7721 cell lines, with IC50 values of 9.10 and 7.50 µM, respectively.

Cytotoxic limonoids from Melia azedarach.

Five new compounds (1-5), including two limonoids, one triterpenoid, one steroid, and one sesquiterpenoid, along with nine known limonoids (6-14), were isolated from the bark of Melia azedarach. The structures of the new compounds were elucidated by 2D NMR spectroscopy and mass spectrometry. The isolated compounds as well as three acetylated derivatives of 9 were evaluated for their cytotoxicities against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480) by an MTT assay. Seven limonoids (1, 6, 7, 8, 9, 9b, and 9c) showed significant inhibitory activities against tested cell lines with IC50 values ranging from 0.003 to 0.555 µM, and their preliminary structure-activity relationships are also discussed.

Melodinines M-U, cytotoxic alkaloids from Melodinus suaveolens.

Nine new alkaloids, melodinines M-U (1-9), and 11 known alkaloids were isolated from Melodinus suaveolens. The new structures were elucidated by extensive NMR and mass spectroscopic analyses and comparison to known compounds. All compounds were evaluated for their cytotoxicity against five human cancer cell lines. Compounds 6, 11, and 16 showed significant cytotoxicity.

Phenolic compounds from the branches of Eucalyptus maideni.

Three new phenolic compounds, eucalmaidin F (1), (3S)-5-guaiacyl-3-hydroxypentanoic acid (2), and 8-ß-C-glucopyranosyl-5,7-dihydroxy-2-isobutylchromone (3), were isolated from the branches of E. maideni, together with 30 known compounds, including four phenylpropanoids, three lignans, four phloroglucinol glucosides, five dihydroflavonoids, seven simple phenolic compounds, six terpenoids, and glycerol. The new structures were established by spectroscopic studies (MS, and 1D- and 2D-NMR), chemical degradation, and modified Mosher's method. Compounds 3, guaiacylglycerol, 3-hydroxy-1-(4-hydroxyphenyl)propan-1-one, caffeic acid, (2E)-3-(4-hydroxyphenyl)prop-2-enoic acid, (7'S,8R,8'R)-lyoniresinol, (+)-lyoresinol 3α-O-α-L-rhamnopyranoside, garcimangosone, phlorocetophenone 2'-glucopyranoside, (+)-taxifolin 3α-O-α-L-rhamnopyranoside, (+)-aromadendrin, (+)-taxifolin, resveratrol, piceatannol, 3,4,5-trihydroxyphenol. Tachiaside, gallic acid, macrocapals A und G, and oleuropeic acid were evaluated for their cytotoxicities against five human cancer cell lines. Resveratrol, piceatannol, gallic acid, and macrocapal G exhibited moderate inhibitory effects on human myeloid heukemia HL-60 cell, with IC(50) values of 22.05, 22.05, 7.75, and 31.93 µM, respectively; and only macrocapal G showed inhibitory effect on hepatocellular carcinoma SMMC-7721 cell, with an IC(50) value of 26.75 µM.

Daphnane-type diterpene esters with cytotoxic and anti-HIV-1 activities from Daphne acutiloba Rehd.

Seven previously unreported daphnane-type diterpene esters named acutilobins A-G, together with 12 known ones, were isolated from EtOAc extract of Daphne acutiloba Rehd. Their structures were elucidated based on the spectroscopic data. The cytotoxic and anti-HIV-1 activities of these daphnane-type diterpene esters were evaluated through bioassays. Fourteen of these isolates exhibited definite cytotoxic activities against the five human tumor cell lines HL-60, SMMC-7721, A-549, MCF-7, and SW480. Additionally, anti-HIV-1 activities were observed in 13 daphnane-type diterpene esters, among which acutilobins A-G exhibited significant anti-HIV-1 activities with EC50 below 1.5 nM and SI over 10,000. Particularly, genkwanineVIII showed the strongest activity with EC50 0.17 nM and SI 187,010.

One new pregnane glycoside from the seeds of cultivated Brucea javanica.

A new pregnane glycoside, named (20R)-O-(3)-ß-D-glucopyranosyl-(1→2)-α-L-arabinopyranosyl-pregn-5-en-3ß,20-diol (1), and seven known compounds, brusatol (2), bruceine B (3), bruceine D (4), yadanziolide A (5), bruceine E (6), yadanzioside G (7), and yadanzioside B (8), were isolated from the cultivated dry seeds of Brucea javanica. The structure of 1 was elucidated on the basis of 1D- and 2D-NMR spectroscopic analyses. Their inhibitory effects on tumor cells were also tested. Compound 1 was slightly active against HL-60, SMMC-7721, A-549, and MCF-7 tumor cells. Compounds 2 and 3 demonstrated significant inhibitory activities against all tested cells. These results indicate that cultivated B. javanica could replace the wild plant as an antitumor plant resource.

Schicagenins A-C: three cagelike nortriterpenoids from leaves and stems of Schisandra chinensis.

Schicagenins A-C (1-3), three unprecedented nortriterpenoids characterized with a tetracyclic oxa-cage motif and C(9) side chain, were discovered from the leaves and stems of Schisandra chinensis. Their structures were determined on the basis of extensive spectroscopic analysis, and the absolute stereochemistries were established by single-crystal X-ray diffraction and CD experiments. A plausible biosynthetic pathway of 1-3 was also discussed.

Design, synthesis and cytotoxic activities of novel ß-amino alcohol derivatives.

Three series of novel ß-amino alcohols possessing an N-anthranyl group have been obtained using tryptophan as the major starting material. These compounds were screened for cytotoxic activity against five human cancer cell lines in vitro by MTT assay, and some of them exhibited potential ability to be anticancer agents. Structure-activity relationship was carefully investigated. Only the compounds possessing small substituents (H or CH(3)) at C-6 position showed the same activity as cisplatin (DDP) did.

Neoclerodane diterpenoids from Scutellaria barbata.

Eight new neoclerodane diterpenoids (1- 8), scutebatas H-O, together with eight known compounds, have been isolated from the whole plant of Scutellaria barbata D. Don. Their structures were elucidated on the basis of spectroscopic studies. In vitro cytotoxicity of selected compounds against cancer cell lines HL-60, SMMC-7721, A-549, MCF-7, and SW480 was evaluated. Compounds 5, 6, 7 showed moderate cytotoxicities against several human cancer cell lines, with IC50 values ranging from 12.6-31.4 µM. In addition, compound 1 showed selective cytotoxicity against MCF-7.

New chalcone and dimeric chalcones with 1,4-p-benzoquinone residue from Combretum yunnanense.

New chalcone and dimeric chalcones with 1,4- P-benzoquinone residue, combrequinone A (1), combrequinone B (2), and combrequinone C (3), along with three known compounds (4-6), were isolated from the ethanolic extract of the stems and leaves of Combretum yunnanense, and their structures were determined by spectroscopic analysis. Compounds 1-3 were evaluated for in vitro cytotoxicity against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7, and SW480. Compounds 1, 2 and 3 were found to be most potent against HL-60 acute leukemia cells, with IC50 values of 4.63, 4.07, and 1.26 µM, respectively.

[PET/CT-based classification of delayed radiation encephalopathy following radiotherapy for nasopharyngeal carcinoma].

OBJECTIVE: To investigate positron-emission tomography-computed tomography (PET/CT) findings of radiation encephalopathy (RE) following radiotherapy for nasopharyngeal carcinoma (NPC), observe the metabolic changes of the compromised brain tissues, and postulate the clinical classification of RE to provide reference for its diagnosis. METHODS: This study included 53 pathologically confirmed NPC patients who received previous radical radiotherapy, and the diagnosis of RE was established according to the clinical manifestations and CT/PET findings. All the patients underwent PET/CT whole-body and head scans, and the image data were evaluated along with the clinical data of the patients. RESULTS: RE most frequently involved the lateral or bilateral inferior temporal lobes. PET identified hypometabolic changes in the bilateral temporal lobes of 35 patients (70 lobes) and in the lateral temporal lobe of 18 patients (18 lobes). According to the PET/CT findings, the lesions were classified into 3 types, namely the oedema type (56 temporal lobes), liquefactive necrosis type (10 temporal lobes), and atrophic calcification type (22 temporal lobes). One patient with oedema type lesion received neurotrophic treatment and recovered completely with normal brain tissue density and metabolism, but the oedema type lesions in 2 patients progressed into to atrophic calcification type; the liquefactive necrotic lesions in another 2 patients also progressed into atrophic calcification type. CONCLUSION: RE patients exhibit significant hypometabolic changes in the inferior temporal lobe on PET. According to the findings by PET/CT, RE can be classified into the oedema type, liquefactive necrosis type, and atrophic calcification type, and lesions of the former two types may progress into the third type.