Chang-Xiang Chen

Lindenane Disesquiterpenoids with Anti-HIV-1 Activity from Chloranthus japonicus

Five new lindenane disesquiterpenoids, chlorajaponilides A-E (1-5), together with 11 known analogues were isolated from whole plants of Chloranthus japonicus. The structure and absolute configuration of 1 was confirmed by X-ray crystallography. Compounds 1 and 2 represent the first examples of lindenane disesquiterpenoids with a C-5 hydroxy group and a C-4-C-15 double bond. Compounds 8, 9, 11, and 12 showed anti-HIV-1 replication activities in both wild-type HIV-1 and two NNRTIs-resistant strains. Shizukaol B (8) exhibited the best activity against HIV(wt), HIV(RT-K103N), and HIV(RT-K103N) with EC₅₀ values of 0.22, 0.47, and 0.50 μM, respectively. Compounds 8, 9, 11, and 12 had significant cytotoxicities against C8166 cells with CC₅₀ values of 0.020, 0.089, 0.047, and 0.022, respectively, and exhibited inhibitory activities against HIV-1 with EC₅₀ values of 0.0014, 0.016, 0.0043, and 0.0033 μM, respectively.

Steroidal saponins with antimicrobial activity from stems and leaves of Paris polyphylla var. yunnanensis

Rhizoma Paridis, the root of Paris polyphylla var. yunnanensis (Trilliaceae), is a Chinese traditional medicine, which resources become less and less. However, the aerial parts of this herb, which can regenerate every year, were discarded. In order to expand the resources, detailed chemical investigation on the stems and leaves of Paris polyphylla var. yunnanensis led to isolation of one sapogenin and 24 steroidal saponins (1-25), including 6 new glycosides, named chonglouosides SL-1-SL-6 (1-6). Their structures were elucidated on the basis of detailed analyses of their 1D and 2D NMR spectra and acid hydrolysis. Among them, compounds 3 and 4 are the first 23,27-dihydroxydiosgenin saponin having a sugar chain attached to C-23 or C-27, while compound 6 is the first 27-hydroxyruscogenin glycoside bearing 1, 27-di-O-sugar chains. The known compounds 10, 12, 14, 19, 20, 22, and 25 were isolated from the genus Paris for the first time. Antimicrobial testing activities of the selected compounds showed that compound 2, 3, 6, 8, 9, 11, 13, 17, 18, 21, and 24 were active against Propionibacterium acnes with MIC values of 62.5, 62.5, 3.9, 16.5, 17.2, 7.8, 39.0, 17.2, 31.3, 62.5, and 31.3 μg/ml, respectively.

Tigliane-Type Diterpenoid Glycosides from Euphorbia fischeriana

Investigation of whole plants of Euphorbia fischeriana afforded three new tigliane-diterpenoid glycosides, fischerosides A-C (1-3), together with 11 known diterpenoids. Fischerosides A-C (1-3) are the first tigliane-type diterpenoid glucosides. Their structures were determined by a combination of 1D and 2D NMR, MS, and acid hydrolysis. Inhibitory activity against HIV-1 was assessed for compounds 1-5. The new compound 3 showed an EC₅₀ value of 0.02 μM and a therapeutic index (TI) of 17.50, while prostratin (4) and 12-deoxyphorbol-13,20-diacetate (5) showed significantly greater anti-HIV-1 activity.

Ypsilandrosides C-G, five new spirostanol saponins from Ypsilandra thibetica.

A further phytochemical investigation on the whole plants of Ypsilandra thibetica yielded one sapogenin and 12 spirostanol saponins. Five of these are new compounds, designated as ypsilandrosides C-G (2-6). Their structures were determined by detailed spectroscopic analysis, including extensive 1D and 2D NMR data, and by the result of a hydrolytic reaction. Compounds 2-5 were rare steroidal saponins that an apiofuranosyl unit was directly linked at C-3 of the aglycone. Selected spirostanol saponins (2-6, 9) were tested for their cytotoxic activities against K562, SPC-A-1, BGC-823, Eca-109, and AGS cell lines. Compounds 6 and 9 showed moderate inhibitory activity against all five cell lines. The antifungal properties of the new spirostanol saponins (2-6) against Candida albicans were also determined.

Steroidal saponins from stems and leaves of Paris polyphylla var. yunnanensis.

Phytochemical investigation of the stems and leaves of Paris polyphylla var. yunnanensis led to isolation of 12 steroidal saponins, chonglouosides SL-9-SL-20, which had not been described previously, along with 13 known compounds. Their structures were established on the basis of extensive spectroscopic analysis and chemical methods. Four of the twelve steroidal saponins possessed three steroidal aglycones which have not been reported in nature. Steroidal saponins were also evaluated for their cytotoxicities against two human cancer cell lines (HepG2 and HEK293) and anti-HCV effects. One known steroidal saponin was the most cytotoxic compound overall with IC50 values of 2.9 ± 0.5 μM and 5.0 ± 0.6 μM against HepG2 and HEK293 cell lines, respectively, while none showed anti-HCV activity at a concentration of 20 μM.

Steroidal saponins with induced platelet aggregation activity from the aerial parts of Paris verticillata

In order to utilize and protect the resources of Rhizoma Paridis rationally, we carried out a phytochemical investigation on the non-medicinal (aerial) parts of Paris verticillata that led to the isolation of fifteen steroidal saponins. Among them, three are new spirostanol saponins, named parisverticosides A–C (1–3), as well as one new cholestane glycoside, named parisverticoside D (4). Their structures were elucidated by extensive spectroscopic analysis and acid hydrolysis. The aglycone of compound 1 is a new spirostane and identified as (23S,24S,25S)-spirost-5-en-1b,3b,23, 24-tetraol. The selected isolates were evaluated for induced platelet aggregation activity and compound 5 showed 62% maximal platelet aggregation rate at the concentration of 300 lg/mL.

Spirostanol tetraglycosides from Ypsilandra thibetica

Phytochemical reinvestigation on the whole plants of Ypsilandra thibetica obtained five new spirostane glycosides, ypsilandrosides H-L (1-5), and a known saponin polyphylloside III (6). Among them, 1 and 2 are the first spirostane glycosides which possess novel 5(6-->7) abeo-steroidal aglycones. Compounds 3 and 4 are rare saponins whose aglycones contain a hydroxyl group at C-7. Their structures were elucidated on the basis of MS, 1D and 2D NMR spectroscopic analysis and chemical evidences. The isolated compounds were evaluated for their cytotoxic activity on five tumor cell lines.

Chloramultiols A-F, Lindenane-Type Sesquiterpenoid Dimers from Chloranthus multistachys

Six new highly complex lindenane-type sesquiterpenoid dimers, chloramultiols A-F (1-6), along with six known analogues, were isolated from the whole plant of Chloranthus multistachys. The structures of 1-6 were elucidated on the basis of mass spectrometry (MS) and 1D and 2D NMR spectroscopic analysis. Among them, compounds 1 and 6 contain a unique 18-membered macrocyclic triester ring. All compounds isolated were evaluated for the inhibition of the growth of five tumor cell lines.

Six new C21 steroidal glycosides from Asclepias curassavica L.

Six new C(21) steroidal glycosides, named curassavosides A-F (3-8), were obtained from the aerial parts of Asclepias curassavica (Asclepiadaceae), along with two known oxypregnanes, 12-O-benzoyldeacylmetaplexigenin (1) and 12-O-benzoylsarcostin (2). By spectroscopic methods, the structures of the six new compounds were determined as 12-O-benzoyldeacylmetaplexigenin 3-O-beta-D-oleandropyranosyl-(1-->4)-beta-D-digitoxopyranoside (3), 12-O-benzoylsarcostin 3-O-beta-D-oleandropyranosyl-(1-->4)-beta-D-digitoxopyranoside (4), sarcostin 3-O-beta-D-oleandropyranosyl-(1-->4)-beta-D-canaropyranosyl-(1-->4)-beta-D-oleandropyranosyl-(1-->4)-beta-D-digitoxopyranoside (5), sarcostin 3-O-beta-D-oleandropyranosyl-(1-->4)-beta-D-canaropyranosyl-(1-->4)-beta-D-canaropyranosyl-(1-->4)-beta-D-digitoxopyranoside (6), 12-O-benzoyldeacylmetaplexigenin 3-O-beta-D-glucopyranosyl-(1-->4)-beta-D-oleandropyranosyl-(1-->4)-beta-D-canaropyranosyl-(1-->4)-beta-d-oleandropyranosyl-(1-->4)-beta-D-digitoxopyranoside (7), and 12-O-benzoylsarcostin 3-O-beta-D-glucopyranosyl-(1-->4)-beta-D-oleandropyranosyl-(1-->4)-beta-d-canaropyranosyl-(1-->4)-beta-D-oleandropyranosyl-(1-->4)-beta-D-digitoxopyranoside (8), respectively. All compounds (1-8) were tested for in vitro cytotoxicity; only compound 3 showed weak inhibitory activity against Raji and AGZY cell lines.

Taccasubosides A–D, four new steroidal glycosides from Tacca subflabellata

By analyzing the steroidal content of fresh whole plants of Tacca subflabellata (Taccaceae), we isolated one sapogenin and eight glycosides with four kinds of steroidal skeletons including four new glycosides, named taccasubosides A-D (1-4), together with five known compounds. Among them, compound 1 is the first pentacyclic sterol glycoside with 6-6-6-5-6 fused rings. The structures of 1-4 were elucidated on the basis of extensive spectroscopic analysis, including that of 2D NMR data, and the results of acidic hydrolysis. The cytotoxicity of the selected steroidal glycosides (1-4, 8, and 9) was evaluated in vitro against five human cancer cell lines. Compound 9 showed significant inhibitory activity against all five cell lines.