Wei-Lie Xiao

Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells

Peroxiredoxins (Prxs) are potential therapeutic targets for major diseases such as cancers. However, isotype-specific inhibitors remain to be developed. We report that adenanthin, a diterpenoid isolated from the leaves of Rabdosia adenantha, induces differentiation of acute promyelocytic leukemia (APL) cells. We show that adenanthin directly targets the conserved resolving cysteines of Prx I and Prx II and inhibits their peroxidase activities. Consequently, cellular H(2)O(2) is elevated, leading to the activation of extracellular signal-regulated kinases and increased transcription of CCAAT/enhancer-binding protein β, which contributes to adenanthin-induced differentiation. Adenanthin induces APL-like cell differentiation, represses tumor growth in vivo and prolongs the survival of mouse APL models that are sensitive and resistant to retinoic acid. Thus, adenanthin can serve as what is to our knowledge the first lead natural compound for the development of Prx I- and Prx II-targeted therapeutic agents, which may represent a promising approach to inducing differentiation of APL cells.

Study on solid phase extraction and graphite furnace atomic absorption spectrometry for the determination of nickel, silver, cobalt, copper, cadmium and lead with MCI GEL CHP 20Y as sorbent.

A solid phase extraction and graphite furnace atomic absorption spectrometry (GFAAS) for the determination of nickel, silver, cobalt, copper, cadmium and lead with MCI GEL CHP 20Y as sorbent was studied. Trace amounts of chromium, nickel, silver, cobalt, copper, cadmium and lead were reacted with 2-(2-quinolinil-azo)-4-methyl-1,3-dihydroxidobenzene (QAMDHB) followed by adsorption onto MCI GEL CHP 20Y solid phase extraction column, and 1.0molL(-1) HNO(3) was used as eluent. The metal ions in 300mL solution can be concentrated to 1.0mL, representing an enrichment factor of 300 was achieved. The recoveries of analytes at pH 8.0 with 1.0g of resin were greater than 95% without interference from alkaline, earth alkaline and some metal ions. When detected with graphite furnace atomic absorption spectrometry, the detection limits in the original samples were 1.4ngL(-1) for Cr(III), 1.0ngL(-1) for Ni(II), 0.85ngL(-1) for Ag(I), 1.2ngL(-1) for Co(II), 1.0ngL(-1) for Cu(II), 1.2ngL(-1) for Cd(II) and 1.3ngL(-1) for Pb(II). The validation of the procedure was performed by the analysis of the certified standard reference materials, and the presented procedure was applied to the determination of analytes in biological, water and soil samples with good results (recoveries range from 89 to 104%, and R.S.D.% lower than 3.2%. The results agreed with the standard value or reference method).

Compounds from Kadsura heteroclita and related anti-HIV activity.

Phytochemical investigation of the stems of Kadsura heteroclita led to isolation of 16 compounds, including the triterpenoid named longipedlactone J (2), and two dibenzocyclooctadiene type lignans named heteroclitin I and J (3, 4). Compounds 8-10, 14, and 15 were weakly active as anti-HIV agents, whereas compounds 6 and 12 exhibited moderate anti-HIV activity with EC50 values of 1.6 microg/mL, and 1.4 microg/mL, therapeutic index (TI) values of 52.9, and 65.9, respectively. Their structures were established by spectroscopic methods, including application of 2D NMR techniques and CD spectra.

Schinalactone A, a New Cytotoxic Triterpenoid from Schisandra sphenanthera

A new cytotoxic triterpenoid, schinalactone A (1), together with two new biogenetically related compounds, schinalactones B (2) and C (3), has been isolated from the roots and stems of Schisandra sphenanthera.Their structures were elucidated on the basis of extensive spectroscopic analysis. Compounds 1 and 2 showed significant cytotoxicity against PANC-1 cell lines with IC(50) values of 5.9 and 4.1 microM, respectively. A plausible biosynthetic pathway of 1 was also postulated.

Nortriterpenoids and lignans from Schisandra sphenanthera

Nortriterpenoids, sphenadilactone C (1) and sphenasin A (2), together with four known lignans (3-6), were isolated from the leaves and stems of Schisandra sphenanthera. Their structures were elucidated by extensive analysis of 1D and 2D NMR spectroscopic data and compound 2 was further confirmed by single-crystal X-ray diffraction. Compound 1 features a partial enol moiety and an acetamide group in its structure. In addition, compounds 1, 3-6 showed weak anti-HIV-1 activity with EC(50) values in the range of 15.5-29.5 microg/mL.

Lignans from Kadsura angustifolia.

Phytochemical investigation of Kadsura angustifolia led to the isolation and identification of 26 lignans and two triterpenoids, including 11 new lignans named kadangustins A-K ( 1- 11). The structures and stereochemistry of 1- 11 were elucidated by analysis of spectroscopic data. Except for 11 and 20, all the lignans were evaluated for their inhibitory activity against HIV-1. Binankadsurin A ( 19) showed anti-HIV activity with an EC 50 value of 3.86 microM.

Cytotoxic ent-kaurane diterpenoids from Isodon rubescens var. lushiensis.

Ten new ent-kaurane diterpenoids, isolushinins A-J (1-10), together with 20 known compounds, were isolated from the aerial parts of Isodon rubescens var. lushiensis. The structures of 1-10 were elucidated by spectroscopic analysis. Several of the compounds isolated were evaluated for their cytotoxicity against the HL-60, SMMC-7721, A-549, SK-BR-3, and PANC-1 human cancer cell lines, and some exhibited quite potent inhibitory activities.

Schilancitrilactones A–C: Three Unique Nortriterpenoids from Schisandra lancifolia

Three unique nortriterpenoids, schilancitrilactones A-C (1-3), were isolated from the stems of Schisandra lancifolia . Compound 1 possesses a 5/5/7/5/5/5-fused hexacyclic ring system with a C(29) backbone, while 2 and 3 feature a C(27) skeleton with a 5/7/5/5/5-fused pentacyclic ring system. Their absolute stereochemistries were established by CD and single-crystal X-ray diffraction experiments. Compound 3 showed anti-HIV-1 activity with an EC(50) value of 27.54 μg/mL, and 1 exhibited antifeedant activity at 15.73 μg/cm(2).

Lignans with Anti-HIV Activity from Schisandra propinqua var. sinensis

Fourteen new lignans, tiegusanins A-N (1-14), together with 13 known compounds were isolated from the aerial parts of Schisandra propinqua var. sinensis. The structures and absolute configurations of 1-13 were established using a combination of spectroscopic techniques. Compound 14 was obtained as a racemate. When evaluated for inhibitory activity against HIV-1, tiegusanin G (7) showed anti-HIV-1 activity with an EC(50) value of 7.9 microM and a therapeutic index (TI) of more than 25.

Propindilactones E-J, Schiartane Nortriterpenoids from Schisandra propinqua var. propinqua

Six new nortriterpenoids, propindilatones E-J (1-6), and two known (7, 8) schiartane-type nortriterpenoids were isolated from the stems of Schisandra propinqua var. propinqua. Their structures were elucidated by extensive spectroscopic analyses, and the structure of compound 4 was confirmed through single-crystal X-ray diffraction. The absolute configuration of compounds 1-3 was established using CD methods. Compounds 4-6 were noncytotoxic against K562, A549, and HT-29 human cancer cells.