Xing-Yao Li

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.

Cytotoxic alkaloids from the whole plants of Zephyranthes candida.

Seven new alkaloids, N-methylhemeanthidine chloride (1), N-methyl-5,6-dihydroplicane (5), O-methylnerinine (6), N-ethoxycarbonylethylcrinasiadine (7), N-ethoxycarbonylpropylcrinasiadine (8), N-phenethylcrinasiadine (9), and N-isopentylcrinasiadine (10), together with eight known alkaloids, hemeanthamin (2), 3-epimacronine (3), (+)-tazettine (4), N-methylcrinasiadine (11), trisphaeridine (12), 5,6-dihydrobicolorine (13), lycorine (14), and nigragillin (15), were isolated from the whole plants of Zephyranthes candida. The structures of the new compounds were established by spectroscopic data interpretation, with single-crystal X-ray diffraction analysis performed on 1. The absolute configuration of 3-epimacronine (3) was determined by single-crystal X-ray diffraction analysis with Cu Kα irradiation. Compounds 1-15 were evaluated for their in vitro cytotoxicity against five human cancer cell lines and the Beas-2B immortalized (noncancerous) human bronchial epithelial cell line. Compounds 1, 2, 9, and 14 exhibited cytotoxicity with IC(50) values ranging from 0.81 to 13 μM with selectivity indices as high as 10 when compared to the Beas-2B cell line.

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.

Henryin, an ent-kaurane diterpenoid, inhibits Wnt signaling through interference with β-catenin/TCF4 interaction in colorectal cancer cells.

Aberrant Wnt/β-catenin signaling has been strongly associated with the tumorigenesis of human colorectal cancer. Inhibitors of this pathway may then offer therapeutic strategies as well as chemoprevention for this malignant disease. Henryin is an ent-kaurane diterpenoid isolated from Isodon rubescens var. lushanensis , a plant long been used in folk medicine to prevent inflammation and gastrointestinal disease. In the present study, we report that henryin selectively inhibits the proliferation of human colorectal cancer cells with a GI50 value in the nano-molar range. Microarray analysis and reporter assays showed that henryin worked as a novel antagonist of Wnt signaling pathway. Henryin reduced the expression of Cyclin D1 and C-myc, and induced G1/S phase arrest in HCT116 cells. Concurrently, henryin did not affect the cytosol-nuclear distribution of soluble β-catenin, but impaired the association of β-catenin/TCF4 transcriptional complex likely through directly blocking the binding of β-catenin to TCF4. We also then analyzed the structure-activity relationship among the ent-kaurane type diterpenoids. Our data suggests that henryin, as a novel inhibitor of Wnt signaling, could be a potential candidate for further preclinical evaluation for colon cancer treatment, and as such warrants further exploration.

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.

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.

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.

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 12.6-31.4u2009µM. In addition, compound 1 showed selective cytotoxicity against MCF-7.

Two mixed-NH3/amine platinum (II) anticancer complexes featuring a dichloroacetate moiety in the leaving group

Two mixed-NH3/amine platinum (II) complexes of 3-dichoroacetoxylcyclobutane-1, 1-dicarboxylate have been prepared in the present study and characterized by elemental analysis and IR, HPLC-MS and 1H, 13C-NMR. The complexes exist in equilibrium between two position isomeric forms and undergo hydrolysis reaction in aqueous solution, releasing the platinum pharmacophores and dichloroacetate which is a small-molecular cell apoptosis inducer. Both complexes were evaluated for in vitro cytotoxic profile in A549, SGC-7901 and SK-OV-3 caner cells as well as in BEAS-2B normal cells. They exhibit markedly cytoxicity toward cancer cells by selectively inducing the apoptosis of cancer cells, whereas leaving normal cells less affected. They have also the ability to overcome the resistance of SK-OV-3 cancer cells to cisplatin. Our findings offer an alternative novel way to develop platinum drugs which can both overcome the drug resistance and selectively target tumor cells.

Experimental study on cracking damage characteristics of a soil and rock mixture by UPV testing

This paper investigates the ultrasonic pulse velocity (UPV), mechanical properties and cracking characteristics of a soil and rock mixture (SRM) with varying rock percentages under uniaxial compression. Cylindrical SRM specimens (50xa0mm diameter and 100xa0mm height) with rock percentages of 20, 30, 40 and 50xa0xa0% were produced to perform a series of uniaxial compressive strength (UCS) tests. A P-wave transducer (500xa0kHz) and associated equipment were employed for all the testing to record the ultrasonic parameters during the whole deformation process. Test results indicates the UCS and UPV decreased with increasing rock percentages for all specimens. The failure mechanism of all specimens showed a splitting-sliding mixed pattern; macro-cracks have a direction of 0°–10° parallel or sub-parallel to the normal stress. In addition, an equation was proposed for the relationship between UPV and crack width. Crack initiation stress was lower for specimens with a high rock percentage. The crack initiation stress level was about 0.2–0.5 times of peak-strength, and the total width of cracks was about 2–5xa0mm at peak-strength. Based on the width of cracks and UPV, the total stress–strain curve was divided into three stages: the linear-elastic stage; the damage initiation and stable development stage; and the damage acceleration stage. Moreover, a three-stage damage evolution equation and constitutive model were established and compared with the testing data. These results confirm that the UPV and mechanical properties of SRMs are closely related to the rock percentage. In this regard, the UPV test can be suitably exploited for determing the cracking evolution characteristics for SRM.