Cucurbitane-Type Triterpene Glycosides from Momordica charantia and Their α-Glucosidase Inhibitory Activities.

Ten cucurbitane-type triterpene glycosides, including five new compounds named charantosides H (1), J (2), K (3), momorcharacoside A (4), goyaglycoside-L (5), and five known compounds (6-10), were isolated from the EtOAc extract of Momordica charantia fruits. The chemical structures of these compounds were identified by 1D and 2D NMR and HRESIMS spectroscopic analyses. Configurations of new compounds were determined by ROESY correlations and comparison of their 13C NMR data with literature reported values. All compounds were evaluated for their inhibition against α-glucosidase, in which compounds 2, 5, 7, 8, 9 showed moderate inhibitory activities with IC50 values ranging from 28.40 to 63.26 µM comparing with the positive control (acarbose, IC50 87.65 ± 6.51 µM).

Virtual Screening and Optimization of Novel mTOR Inhibitors for Radiosensitization of Hepatocellular Carcinoma.

BACKGROUND: Radiotherapy has an ameliorative effect on a wide variety of tumors, but hepatocellular carcinoma (HCC) is insensitive to this treatment. Overactivated mammalian target of rapamycin (mTOR) plays an important part in the resistance of HCC to radiotherapy; thus, mTOR inhibitors have potential as novel radiosensitizers to enhance the efficacy of radiotherapy for HCC. METHODS: A lead compound was found based on pharmacophore modeling and molecular docking, and optimized according to the differences between the ATP-binding pockets of mTOR and PI3K. The radiosensitizing effect of the optimized compound (2a) was confirmed by colony formation assays and DNA double-strand break assays in vitro. The discovery and preclinical characteristics of this compound are described. RESULTS: The key amino acid residues in mTOR were identified, and a precise virtual screening model was constructed. Compound 2a, with a 4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine scaffold, exhibited promising potency against mTOR (mTOR IC50=7.1 nmol/L (nM)) with 126-fold selectivity over PI3Kα. Moreover, 2a significantly enhanced the sensitivity of HCC to radiotherapy in vitro in a dose-dependent manner. CONCLUSION: A new class of selective mTOR inhibitors was developed and their radiosensitization effects were confirmed. This study also provides a basis for developing mTOR-specific inhibitors for use as radiosensitizers for HCC radiotherapy.

Cytotoxic Limonoids from the Twigs and Leaves of Toona ciliata.

Eight new limonoids, toononoids A-H (1-8), eight new B-seco-29-norlimonoids, toonanoronoids A-H (9-16), and seven known analogues were obtained from the EtOAc extract of the twigs and leaves of Toona ciliata. Compounds 2, 4, 8, and 16 are rare lactam-bearing limonoids. Compounds 1, 14, and 15 possess an unusual γ-methoxybutenolide moiety at C-17, while compounds 9, 10, and 15 have a rare 3ß-hydroxy group. Their 2D structure and relative configurations were identified using spectroscopic data. The absolute configurations of 1, 9, 14, and 15 were established via X-ray diffraction crystallography or comparison of experimental and calculated ECD data. The cytotoxicity of the compounds was assessed toward five human tumor cell lines, and their anti-inflammatory activity was assessed based on NO production using LPS-stimulated RAW264.7 macrophages. Compounds 11 and 12 exerted inhibition toward two tumor cell lines (MCF-7, SW-480) with IC50 values between 2.1 and 3.7 µM, while 18-22 inhibited the proliferation of HL-60, MCF-7, and SW-480 cells (IC50 0.6-4.0 µM). Only compound 4 exhibited weak anti-inflammatory activity with an IC50 value of 28.3 µM.

Cytotoxicity of Triterpenoid Alkaloids from Buxus microphylla against Human Tumor Cell Lines.

Three new triterpenoid alkaloids, namely buxmicrophyllines P-R (1-3), were isolated from the twigs and leaves of Buxus microphylla. Their structures were elucidated on the basis of NMR and MS spectroscopic analyses. Structurally, compounds 1-3 belong to the 9,10-cycloartane type alkaloids. In addition, compound 3 exhibited moderate cytotoxic activities in vitro against HL-60, SMMC-7221, A-549, MCF-7, and SW480 cell lines (with IC50 values ranging from 4.51 to 15.58 µM).

[Influence of C-Fe Lines Interference Correction on Laser-Induced Breakdown Spectroscopy Measurement of Unburned Carbon in Fly Ash].

In coal-fired plants, Unburned carbon (UC) in fly ash is the major determinant of combustion efficiency in coal-fired boiler. The balance between unburned carbon and NO(x) emissions stresses the need for rapid and accurate methods for the measurement of unburned carbon. Laser-induced breakdown spectroscopy (LIBS) is employed to measure the unburned carbon content in fly ash. In this case, it is found that the C line interference with Fe line at about 248 nm. The interference leads to C could not be quantified independently from Fe. A correction approach for extracting C integrated intensity from the overlapping peak is proposed. The Fe 248.33 nm, Fe 254.60 nm and Fe 272.36 nm lines are used to correct the Fe 247.98 nm line which interference with C 247.86 nm, respectively. Then, the corrected C integrated intensity is compared with the uncorrected C integrated intensity for constructing calibration curves of unburned carbon, and also for the precision and accuracy of repeat measurements. The analysis results show that the regression coefficients of the calibration curves and the precision and accuracy of repeat measurements are improved by correcting C-Fe interference, especially for the fly ash samples with low level unburned carbon content. However, the choice of the Fe line need to avoid a over-correction for C line. Obviously, Fe 254.60 nm is the best

Identification and antifeedant activities of limonoids from Azadirachta indica.

Four new limonoids, azadiraindins A-D (1-4, resp.), together with seven known analogs, were isolated from the MeOH extract of Azadirachta indica. The structures of 1-4 were elucidated by NMR and MS spectroscopic analyses, and the relative configuration of 1 was determined by single-crystal X-ray crystallography. The compounds isolated in comparatively large amount were evaluated for their antifeedant activities against Plutella xylostella; the antifeedant rate of 10 was 90.6% and the corrected mortality of 8 was 79.2%.

The antigluconeogenic activity of cucurbitacins from Momordica charantia.

Five new cucurbitacins, kuguacins II-VI (1-5), along with five known analogues (6-10), were obtained from the fruit of Momordica charantia. Structures of the new compounds were elucidated as 5ß,19-epoxycucurbit-23-en-7-on-3ß,25-diol (1), 5ß,19-epoxycucurbit-7,23-dion-3ß,25-diol (2), 5ß,19-epoxycucurbit-6-en-19,23-dion-3ß,25-diol (3), 5ß,19-epoxy-23,24,25,26,27-pentanorcucurbit-6-en-7,19-dion-3ß,22-diol (4), and cucurbit-5-en-7,23-dion-3ß,19,25-triol (5) by extensive spectroscopic and single-crystal X-ray diffraction analyses. Some cucurbitane compounds from this species were screened for their potential antidiabetic properties in terms of antigluconeogenic activity. As a result, compounds 1, 10, 11, and 12 (at 25-100 µM) showed concentration-dependent inhibition on glucose production from liver cells. In addition, compounds 11 and 12 (at 100 µM) showed around 20-30 % inhibition on PEPCK activity.

Three new limonoids from Azadirachta indica.

Three new limonoids, azadiraindins E-G (1-3, respectively), together with six known analogs, were isolated from the fresh fruit coats of Azadirachta indica. The structures of these compounds were elucidated by spectroscopic methods (IR, MS, HR-ESI-MS, 1D NMR, and 2D NMR).

Cucurbitane-type triterpenoids from the stems and leaves of Momordica charantia.

Six new cucurbitane-type triterpenoids, karavilagenin F (1), karavilosides XII and XIII (2, 3), momordicines VI, VII, and VIII (4, 5 and 6), along with four known ones, 5ß,19-epoxy-25-methoxycucurbita-6,23-diene-3ß,19-diol (7), 5ß,19-epoxycucurbita-6, 23-diene-3ß,19,25-triol (8), kuguacin R (9), and (19R,23E)-5ß,19-epoxy-19-methoxycucurbita-6,23,25-trien-3ß-ol (10), were isolated from the stems and leaves of Momordica charantia L. Their chemical structures were elucidated by extensive 1D NMR and 2D NMR (HSQC, HMBC, COSY, and ROESY), MS experiments, and CD spectrum. Compound 6 showed weak cytotoxicity against five human cancer cells lines with IC50 values of 14.3-20.5µmol/L.

Chukfuransins A-D, four new phragmalin limonoids with ß-furan ring involved in skeleton reconstruction from Chukrasia tabularis.

Four new phragmalin limonoids (chukfuransins A-D) were isolated from the twigs and leaves of Chukrasia tabularis. Chukfuransins A (1) and B (2) feature a unique C-15/C-20 linkage proposed to be built by a biogenetic pathway involving Michael addition. Chukfuransins C (3) and D (4) feature the C-15/C-21 linkage. Their structures and absolute configurations were established by NMR techniques and X-ray crystallographic analysis.

Studies on the constituents of Cimicifuga foetida collected in Guizhou Province and their cytotoxic activities.

Two new triterpenoids and a chromone glycoside, namely, 24-epi-cimigenol-3-one (1), foetinoside (2), cimifugin-4'-O-[6″-feruloyl]-ß-D-glucopyranoside (3), together with 18 known compounds, were isolated from the rhizomes of Cimicifuga foetida L. collected in Guizhou Province, China. All of the compounds were identified by spectroscopic methods, as well as chemical methods. In the in vitro cytotoxicity evaluation of these compounds against 5 human cancer cell lines, cimigenol (8) exerted the most potent cytotoxic activity against SMMC-7721 (7.87 µM) and A-549 (12.16 µM), while cimiacerin B (9) also showed obvious cytotoxicity against the A-549 cell line, with an IC(50) value of 16.77 µM.

[Evidence for determining the safe surgical margin for pleomorphic adenoma of parotid gland].

OBJECTIVE: To compare the treatment outcomes, complications and histopathologic features between conventional parotidectomy and functional regional parotidectomy in the treatment for pleomorphic adenoma of parotid gland and to provide clinical, and pathological evidence for determining the safe surgical margin. METHODS: Of 109 patients, 60 patients received conventional parotidectomy and 49 patients received functional regional parotidectomy. The rates of tumor recurrence and complications were compared between the groups of patients. RESULTS: There was no significant difference in the incidence of tumor recurrence, the facial paralysis and sialosyrinx between two groups. The rates of Frey's syndrome, numbness of auricular region, and facial asymmetry were 30.0%, 61.7%, and 38.3% in the patients with conventional parotidectomy respectively, while the rates were 6.1%, 30.6%, and 8.2% in the patients with functional regional parotidectomy, with significant statistically difference, respectively (P < 0.05). Of 109 patients, 33 with incomplete capsule, 29 with capsule penetration, 25 with pseudopodia, and 13 with satellite nodules. There was no significant difference in the depth of tumor infiltration between two groups of patients. For the tumor smaller than 2 cm, the depth of infiltration in conventional group was from 0.061 to 1.122 mm, functional group was from 0.442 to 3.127 mm (Z = -1.093, P = 0.057); for the tumors between 2 - 4 cm, the depth in conventional group was from 0.081 to 7.908 mm, functional group was from 0.082 to 6.632 mm (Z = -0.214, P = 0.831); for the tumor larger than 4 cm, the depth of infiltration was from 0.340 to 8.476 mm. CONCLUSIONS: Compared with conventional parotidectomy, functional regional parotidectomy has good outcomes and less complications. The surgical margins of pleomorphic adenomas of the parotid gland should be determined by the size of tumor. The 1 cm-surgical margins are safe for the tumors less than 4 cm, and the tumors more than 4 cm should be treated with superficial parotidectomy.

Limonoids from the leaves of Toona ciliata var. yunnanensis.

Twelve limonoids, toonayunnanins A-L (1-12) and eleven known compounds (13-23) were isolated from the leaves of Toona ciliata var. yunnanensis, and their structures were elucidated by means of extensive spectroscopic analyses, particularly 1D and 2D NMR techniques. The inhibitory effects of all the isolated compounds were evaluated on human tumor cell lines, such as HL-60, SMMC-7721, A-549, MCF-7 and SW480. Cedrelone (13) and dysobinin (18) showed significant cytotoxicity, and toonayunnanin B (2) and epoxyazadiradione (14), were found to be slightly cytotoxic against the above cell lines. Furthermore, this study provides valuable information for the chemotaxonomy of T. ciliata varieties.

Limonoids from the leaves of Swietenia macrophylla.

One new limonoid of the phragmalin type (1) named Swietenine J with nine known compounds methyl-6-ß-hydroxy angolensate (2), 1-O-acetylkhayanolide A(3), Khayanolide E (4), Khayalactone (5), Khayanone (6), 1-O-Acetylkhayanolide B (7), 1-O-Deacetylkhayanolide E (8), Khayanolide A (9), Khayanolide B (10) were isolated from Swietenia macrophylla. The structure of 1 was elucidated on the basis of 1D and 2D- NMR spectroscopic analysis.

[Meta-analysis of surgical techniques for preventing Frey syndrome and a concave facial deformity after parotidectomy].

OBJECTIVE: To explore the curative effects on surgical methods for the prevention of Frey syndrome and a concave facial deformity after parotidectomy. METHODS: A literature search was performed using the Wianfang Database, Chinese Biomedical Literature Disk Database, Chinese Digital Hospital Library and Chinese Scientific Journals Database of VIP from January 1989 to December 2008. Twenty-six Chinese language controlled studies involving surgical techniques for prevention of Frey syndrome and the concave facial deformity after parotidectomy were identified. Review manager 4.2 software was applied for Meta analysis. RESULTS: Meta-analysis for surgical techniques to prevent symptomatic Frey syndrome, a positive starch-iodine test, and contour deformity, favored intervention with a cumulative odds ratio (OR) of 0.14 [95% confidence interval (CI), 0.07-0.25]; OR, 0.21 (95% CI, 0.17-0.26); and OR, 0.09 (95% CI, 0.04-0.19), respectively. There was a significant difference in the incidence of these complications between surgical treatment groups and control groups (Z = 6.42, Z = 13.70, Z = 6.43, all P < 0.05). The application of a sternocleidomastoid muscle flap decreased the incidence of symptomatic Frey syndrome (Z = 2.33, P < 0.05), positive starch-iodine test (Z = 7.48, P < 0.05) and contour deformity (Z = 7.78, P < 0.05). The application of acellular dermal matrix decreased the incidence of symptomatic Frey syndrome (Z = 6.02, P < 0.05) and positive starch-iodine test (Z = 5.72, P < 0.05) but did not decrease the incidence of contour deformity (Z = 1.27, P > 0.05). CONCLUSIONS: Meta-analysis of operative techniques to prevent symptomatic Frey syndrome, a positive starch-iodine test, and facial asymmetry suggests that such methods are likely to reduce the incidence of these complications and improve the quality of life after parotidectomy.

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.

Cycloartane triterpenoids from the aerial parts of Cimicifuga foetida Linnaeus.

Cycloartane triterpenoids, 2',24-O-diacetylisodahurinol-3-O-α-L-arabinopyranoside, 24-O-acetylisodahurinol-3-O-α-L-arabinopyranoside, 12ß-hydroxy-25-anhydrocimigenol, cimigenol-12-one, 12ß-hydroxy-15-deoxycimigenol, 2'-O-acetyl-24-epi-cimigenol-3-O-α-L-arabinopyranoside, 2'-O-acetylcimigenol-3-O-ß-D-xylopyranoside, 25-anhydrocimigenol-3-O-α-L-arabinopyranoside, 2',23-O-diacetylshengmanol-3-O-α-L-arabinopyranoside, and 2',24-O-diacetyl-25-anhydrohydroshengmanol-3-O-α-L-arabinopyranoside, together with eight known compounds, were isolated from aerial parts of Cimicifuga foetida. Their structures were determined by application of spectroscopic analyses and chemical methods. Biological evaluation of the compounds against human HL-60, SMMC-7721, A549, SK-BR-3, and PANC-1 cell lines indicated that three of these compounds exhibited broad-spectrum and moderate cytotoxic activities, with IC50 values ranging from 6.20 to 22.74 µM. By comparing previous cytotoxic testing data and bioassay results from this study, preliminary structure-activity relationships of compounds with a c imigenol-skeleton can be proposed.

Cytotoxic steroids from Sarcococca saligna.

Two new C21-steroidal esters, sarsaligates A(1) and B(2), and two new steroidal alkaloids, sarsaligenines A(3) and B(4), together with four known compounds (sarcovagine, sarcorucinine, dimethylamino-3 ß-pregnane-20-one, and ß-sitosterol 5- 8, respectively), were isolated from the leaves and stems of Sarcococca saligna. The structures of compounds 1-4 were elucidated by NMR and MS spectroscopic analysis. Of the compounds tested, 5 and 6 were the most cytotoxic against the cell lines K562, SK-BR-3, and PANC-1, with IC50 values in the range of 2.25-5.00 µM, while 3 and 4 selectively inhibited HL-60 cells with IC50 values of 2.87 and 3.61 µM, respectively. Compounds 3-6 therefore deserve further evaluation of their cytotoxic potentials.

Three steroids with unique structural feature of 5ß-Spirostan-1ß,3ß,17α-trihydroxyl from Reineckia carnea.

A new spirostanol sapogenin and two spirostanol saponins, tentatively named reineckiagenin A (1), reineckiagenoside A (2), and reineckiagenoside B (3), were isolated from the whole plant of Reineckia carnea. By detailed analysis of their 1D and 2D NMR spectra, chemical methods, and by comparison with spectra data of known compounds, the structures of the new steroids were determined to be 25(S)-5ß-spirostan-1ß,3ß,17α-triol (1), 25(S)-5ß-spirostan-1ß,3ß,17α-triol 1-O-ß-D-xylopyranoside (2), 25(S)-5ß-spirostan-1ß,3ß,17α-triol 1-O-α-L-rhamnopyranosyl-(1→2)-ß-D-xylopyranoside (3). Compounds 1, 2, and 3 are the first naturally occurring steroids with unique structural feature of 5ß-spirostan-1ß,3ß,17α-trihydroxyl.