Lanicepines A and B, Sesquiterpenes with Amino Acid-Derived Substituents from the Flowering Aerial Parts of Saussurea laniceps.

Two new guaianolide sesquiterpenes, lanicepines A (1) and B (2), possessing unusual amino acid-derived substituents at C-13, were isolated from the flowering aerial parts of Saussurea laniceps, a traditional herbal medicine also known as "snow lotus". The structures of 1 and 2 were elucidated based on spectroscopic analysis including applications of the modified Mosher's method and Marfey's method as well as ECD calculations. Lanicepine A (1) contains a dihydropyridinone moiety with a carbamoyl and a hydroxymethyl group. This substituent was considered to consist of asparagine and a C4 unit. In contrast, lanicepine B (2) has a substituent that seems to be derived from l-proline and a C4 unit. Lanicepines A (1) and B (2) and two related known sesquiterpenes isolated from the same plant material, 11ß,13-dihydrodesacylcynaropicrin (3) and 11ß,13-dihydrodesacylcynaropicrin 8-O-ß-d-glucoside (4), demonstrated inhibitory activity against IL-1ß production from LPS-stimulated microglial cells.

Coleifolides A and B, Two New Sesterterpenoids from the Aerial Parts of Scutellaria coleifolia H.Lév.

Coleifolides A and B (1 and 2), two new sesterterpenoids with a ß-methyl-α,ß-unsaturated-γ-lactone moiety, were isolated from the aerial parts of Scutellaria coleifolia H.Lév. (Lamiaceae), together with three known compounds. Their structures were elucidated by NMR and MS examinations. Coleifolides A and B were concluded to be partially racemic compounds by the HPLC analysis using a chiral column or introduction of chiral derivatizing agents. The absolute configuration of the major isomer was determined by analyses of the CD spectrum as well as NMR data of (R)- and (S)-2-NMA derivatives. Coleifolides A and B are structurally similar to manoalide derivatives, previously isolated from marine sponges, and appear to be the first examples of this type of compounds being isolated from higher plants.

Prenylated flavonoids from the roots of Desmodium caudatum and evaluation of their antifungal activity.

Two new prenylated flavonoids (1, 4) and two new prenylated C-methyl-flavonoids (6, 7), together with four known flavonoids (2, 3, 5, 8), were isolated from the roots of Desmodium caudatum. The structures of the new compounds were elucidated by extensive spectroscopic analyses including 1D-, 2D-NMR and MS. The antifungal activities of five compounds (1, 2, 4, 6, 8) as well as nine flavonoids (9-17) previously isolated from this plant against Aspergillus niger, Penicillium sp., Rhizopus sp., and Trichophyton sp. were evaluated. Compound 6 showed potent antifungal activity against Trichophyton sp. with a minimum inhibitory concentration (MIC) value of 1.95 µg/mL.

Lignans from Schisandra propinqua with inhibitory effects on lymphocyte proliferation.

Seven new dibenzocyclooctadiene lignans, named propinquain E-K, together with 11 known lignans were isolated from the ethanol extract of the roots of Schisandra propinqua subsp. sinensis. The structures of the new compounds were elucidated by spectroscopic methods, including ¹H- and ¹³C-NMR, 2D-NMR, HR ESI-MS, and CD spectra. Two dibenzocyclooctadienes revealed inhibitory effects on lymphocyte proliferation.

Sesquiterpene lactone glycosides from the roots of Ferula varia.

Seven new sesquiterpene lactone glycosides (1-7) were isolated from the H2O-soluble fraction from the MeOH extract of the roots of Ferula varia. Their structures were elucidated by extensive spectroscopic analyses. The absolute configurations of compounds 1 and 2 were determined by modified Mosher's method.

New 29-nor-cycloartanes with a 3,4-seco- and a novel 2,3-seco-structure from the leaves of Sinocalycanthus chinensis.

Eight new triterpenoids, including sinocalycanchinensins A-E (1-5) with a 3,4-seco-29-nor-cycloartane skeleton, sinocalycanchinensin F (6) possessing a novel 2,3-seco-29-nor-cycloartane skeleton, and 29-nor-cycloartanes, sinocalycanchinensins G and H (7 and 8), have been isolated from the leaves of Sinocalycanthus chinensis. Their structures were elucidated on the basis of spectroscopic examinations. The cytotoxicities of the isolated new triterpenes against a panel of human cancer cell lines, including multi-drug resistant (MDR) cancer cell lines, were also evaluated. Compound 5 demonstrated enhanced cytotoxicity against MDR KB cells in the presence of colchicine, although all the compounds showed moderate or no cytotoxicities.

Dyscusins A-C, three new steroids from the leaves of Dysoxylum cumingianum.

Three new steroids dyscusins A-C (1-3), including a stigmastane-type sterol and two pregnanes, together with two known steroids were isolated from the leaves of Dysoxylum cumingianum (Meliaceae). Their structures were elucidated on the basis of extensive spectroscopic analyses. In a cytotoxicity assay, compound 1 showed ten-fold enhanced cytotoxicity against multi-drug resistant cancer cells (KB-C2) in the presence of 2.5 µM colchicine as compared with the absence of colchicine. This notable finding indicated that 1 possessed a multi-drug resistant reversal effect.

Spicachlorantins G-J, new lindenane sesquiterpenoid dimers from the roots of Chloranthus spicatus.

Four new lindenane sesquiterpenoid dimers, spicachlorantins G-J (1-4), were isolated from the roots of Chloranthus spicatus together with seven known compounds, including chloramultilide A, shizukaol B, shizukaol D, shizukaol F, shizukaol P, chlorahololide D, and cycloshizukaol A. The planar structures of the new compounds were established by 1D-, 2D-NMR, and MS analyses. The absolute configurations of these compounds were determined by analyzing rotating Overhauser enhancement and exchange spectroscopy (ROESY) and circular dichroism (CD) spectra.

Isolation of novel phenolic compounds with multidrug resistance (MDR) reversal properties from Onychium japonicum.

We isolated seven novel compounds, namely, 3',4',6-trihydroxy-2,4-dimethoxy-3-(3″,4″-dihydroxybenzyl)chalcone (1), 3',6-dihydroxy-2,4,4'-trimethoxy-3-(3″,4″-dihydroxybenzyl)chalcone (2), α,ß-dihydro-3',6-dihydroxy-2,4,6'-trimethoxy-3-(3″,4″-dihydroxybenzyl)chalcone (3), 3',4,4'-trihydroxy-2,6-dimethoxychalcone (4), 4',5,7-trihydroxy-6-(3″,4″-dihydroxybenzyl)flavone (5), 3-(3',4'-dihydroxybenzyl)-6,7-dihydroxycoumarin (6), 3-(3',4'-dihydroxyphenyl)-3,4-dihydroisocoumarin (7), as well as a known compound, 3',4',7-trihydroxy-5-methoxyflavanone (8) from the whole grass of Onychium japonicum, and elucidated their structures by spectroscopic methods. Compounds 1-3 exhibited significant multidrug resistance (MDR) reversal effects on MCF-7/ADR and Bel-7402/5-Fu cell lines.

Petiolins J-M, prenylated acylphloroglucinols from Hypericum pseudopetiolatum var. kiusianum.

Four new prenylated acylphloroglucinols, petiolins J-M (1-4), were isolated from aerial parts of Hypericum pseudopetiolatum var. kiusianum, and the structures were elucidated by spectroscopic data and a single-crystal X-ray diffraction analysis. Petiolin J (1) exhibited antimicrobial activity.

Papyriferic acid derivatives as reversal agents of multidrug resistance in cancer cells.

Forty-one derivatives of papyriferic acid were prepared based on our previous finding that methyl papyriferate (3) showed potent reversing effect on cytotoxicity of colchicine against multidrug resistance (MDR) human cancer cells (KB-C2), and evaluated for their cytotoxicity and effect on reversing P-gp-mediated MDR against KB-C2 cells. 3-O-(Morpholino-beta-oxopropanoyl)-12beta-acetoxy-3alpha,25-dihydroxy-(20S,24R)-epoxydammarane (37) significantly increased the sensitivity of colchicine against KB-C2 cells by 185-fold at 5microg/mL (7.4microM), and the cytotoxicity of colchicine was recovered to nearly that of sensitive (KB) cells. The other several new amide derivatives also exhibited potent reversal activity comparable to or more potent than methyl papyriferate and verapamil.

Conjugates of betulin derivatives with AZT as potent anti-HIV agents.

Fourteen novel conjugates of 3,28-di-O-acylbetulins with AZT were prepared as anti-HIV agents, based on our previously reported potent anti-HIV triterpene leads, including 3-O-acyl and 3,28-di-O-acylbetulins. Nine of the conjugates (49-53, 55, 56, 59, and 60) exhibited potent anti-HIV activity at the submicromolar level, with EC(50) values ranging from 0.040 to 0.098muM in HIV-1(NL4-3) infected MT-4 cells. These compounds were equipotent or more potent than 3-O-(3',3'-dimethylsuccinyl)betulinic acid (2), which is currently in Phase IIb anti-AIDS clinical trial.

Immunosuppressive sesquiterpenes from Buddleja daviddi.

Six new sesquiterpenes, 2,6(12),10-humulatrien-7ß-ol-1-one (1), 2 α-acetoxy-5α-methoxy-enantio-caryophylla-8(15)-en-3-one (2), 2α-acetoxy-5α-hydroxy-enantio-caryophylla-8(15)-en-3-one (3), 2α-acetoxy-4ß,5α-hydroxy-enantio-caryophylla-8(15)-en-3-one ( 4), 2α-acetoxy-4ß,5ß-hydroxy-enantio-caryophylla-8(15)-en-3-one (5), 2ß-acetoxy-4-caryophyllen-8ß-ol-3-one (6), and nineteen known compounds were isolated from the ethanol extract of Buddleja daviddi. The structures were elucidated by spectroscopic methods. Compounds 8-11, 14, 16, 17, and 20 showed significant immunosuppressive activities, and 8-11 and 14 were cytotoxic on HeLa and L929 cell lines.

Chromone and chromanone glucosides from Hypericum sikokumontanum and their anti-Helicobacter pylori activities.

Chromone glucosides, takanechromones A-C (1, 2 and 5) and chromanone glucosides, named takanechromanones A and B (3 and 4), were isolated from the methanolic extracts of Hypericumsikokumontanum together with 27 known compounds. Their structures were established based on spectroscopic evidence. The isolated compounds and some chromone derivatives were assayed for antimicrobial activity against Helicobacter pylori and cytotoxicity against human cancer cell lines.

Acylphloroglucinol, biyouyanagiol, biyouyanagin B, and related spiro-lactones from Hypericum chinense.

Biyouyanagiol (1), an acylphloroglucinol-related compound having a unique cyclopenta-1,3-dione moiety, was isolated from a Japanese traditional medicinal plant, Hypericum chinense, together with three new spiro-lactone-related derivatives, biyouyanagin B (2), 5,6-dihydrohyperolactone D (3), and 4-hydroxyhyperolactone D (4). Their structures were established on the basis of spectroscopic evidence. In a cytotoxicity assay against human cancer cell lines including multidrug-resistant (MDR) cancer cell lines, several compounds demonstrated enhanced cytotoxicity against MDR KB cells in the presence of colchicine.

Petiolins F-I, benzophenone rhamnosides from Hypericum pseudopetiolatum var. kiusianum.

Four new benzophenone-O-rhamnosides, petiolins F-I (1-4), were isolated from aerial parts of Hypericum pseudopetiolatum var. kiusianum, and the structures were elucidated by spectroscopic data and chemical means.

Triterpenes from Astilbe chinensis.

Six new triterpenes, 3beta,6beta-dihydroxyurs-12-en-27-oic acid (1), 3beta,6beta,24-trihydroxyurs-12-en-27-oic acid (2), 3beta,6beta,7alpha-trihydroxyurs-12-en-27-oic acid (3), 3beta-acetoxy-6beta-hydroxyurs-12-en-27-oic acid (4), 3beta,6beta,24-trihydroxyolean-12-en-27-oic acid (5), and 3beta,6beta,7alpha-trihydroxyolean-12-en-27-oic acid (6), were isolated from the rhizomes of Astilbe chinensis. Their structures were elucidated on the basis of 1D- and 2D-NMR analyses and HR-MS experiments. The isolated compounds exhibited significant cytotoxic activities against the SK-N-SH and HL-60 cell lines.

Cytotoxic triterpene saponins from Alternanthera philoxeroides.

Four new pentacyclic triterpene saponins, philoxeroidesides A-D (1-4) were isolated from the aerial parts of Alternanthera philoxeroides. Their structures were elucidated on the basis of 1D- and 2D-NMR experiments and MS analyses. Philoxeroidesides A-D (1-4) showed cytotoxic activities against SK-N-SH and HL60 cell lines.

Tomoeones A-H, cytotoxic phloroglucinol derivatives from Hypericum ascyron.

Phloroglucinol derivatives tomoeones A-H (1-8) and three known compounds were isolated from leaves of Hypericum ascyron. Their structures were established based on spectroscopic analyses. They are all acylphloroglucinol derivatives possessing a spiro skeleton with geminal isoprenyl groups and a monoterpene moiety, and they are stereoisomers to each other at C-4 and C-13. They appear to be a class of phloroglucinol derivatives. Cytotoxicities of the isolated phloroglucinol derivatives against human tumor cell lines, including multidrug-resistant (MDR) cancer cell lines, were evaluated. Tomoeone F (6) demonstrated significant cytotoxicity against KB cells with an IC50 value of 6.2 microM. Compound 6 was also cytotoxic against MDR cancer cell lines (KB-C2 and K562/Adr), which was more potent than doxorubicin.

Monoterpene glycosides from Paeonia hybrida.

Monoterpene glycosides (1-5, and 7), together with 14 known compounds, were isolated from the methanol extract of the roots of Paeonia hybrida. These compounds included a paeoniflorin-related glycoside with a hybrid structure of paeoniflorin and paeonovicinoside (1), a monoterpene glucoside biogenetically related to lactiflorin (2), a paeoniflorin-related monoterpene (3), arbiflorin-related monoterpenes (4 and 5), and a tymol-related monoterpene glycoside (7). Their structures were elucidated by extensive spectroscopic examinations.