Chung Ren Su

Anti-HBV and cytotoxic activities of pyranocoumarin derivatives.

Four natural pyranocoumarins clausenidin (1), nordentatin (2), clausarin (3), and xanthoxyletin (4) were isolated from the medicinal plant Clausena excavata. Recently, we found that 1 and 2 suppressed hepatitis B virus surface antigen in HepA2 cells, and in addition, 1-3 showed cytotoxic activity against four human cancer cell lines (A549, MCF7, KB, and KB-VIN). To explore the SAR of 1-4, 17 pyranocoumarin analogues (5-21) were designed and synthesized. Among these analogues, 5 and 10 were the most potent against hepatitis B virus with EC(50) values of 1.14 and 1.34microM, respectively. The most interesting result in the cytotoxicity assay was the significant activity of 1, 5, and 6 against the multi-drug resistant cell line, KB-VIN, without activity against the KB cell line. These data suggest that these three compounds could be useful hits for developing MDR-inverse drugs.

Design, synthesis, and biological evaluation of Mannich bases of heterocyclic chalcone analogs as cytotoxic agents

The chalcone skeleton (1,3-diphenyl-2-propen-1-one) is a unique template that is associated with various biological activities. We synthesized Mannich bases of heterocyclic chalcones (9-47) using a one-step Claisen-Schmidt condensation of heterocyclic aldehydes with Mannich bases of acetophenones, and tested the target compounds for cytotoxicity against three human cancer cell lines (prostate, PC-3; breast, MCF-7; nasopharynx, KB) and a multi-drug resistant subline (KB-VIN). Out of the 39 chalcones synthesized, 31 compounds showed potent activity against at least one cell line with IC(50) values ranging from 0.03 to 3.80 microg/mL. Structure-activity relationships (SAR) are also discussed.

Flavonoids and ent-labdane diterpenoids from Andrographis paniculata and their antiplatelet aggregatory and vasorelaxing effects

Two new flavones, designated as andropaniculosin A (1) and andropaniculoside A (2), and 30 known compounds were isolated as a result of detailed chemical examination on the whole plants of Andrographis paniculata. Their structures have been elucidated mainly by 1D and 2D NMR, and MS spectroscopic methods. Among them, four flavonoids showed potent inhibition of collagen, arachidonic acid, thrombin, and platelet activation factor induced platelet aggregation. Furthermore, a diterpenoid demonstrated moderate vasorelaxing effect in isolated rat thoracic aorta.

Total synthesis of phenanthroindolizidine alkaloids (+/-)-antofine, (+/-)-deoxypergularinine, and their dehydro congeners and evaluation of their cytotoxic activity.

Due to their limited natural abundance and significant biochemical effects, we synthesized the alkaloids (+/-)-antofine (1a), (+/-)-deoxypergularinine (1b), and their dehydro congeners (2 and 3) starting from the corresponding phenanthrene-9-carboxaldehydes. We also evaluated their in vitro cytotoxic activity. Compounds 1a and 1b showed significant potency against various human tumor cell lines, including a drug-resistant variant, with EC(50) values ranging from 0.16 to 16ng/mL. Structure-activity correlations of these alkaloids and some of their synthetic intermediates were also ascertained. The non-planar structure between the two major moieties, phenanthrene and indolizidine, plays a crucial role in the cytotoxic activity of phenanthroindolizidines. Increasing the planarity and rigidity of the indolizidine moiety significantly reduced potency. A methoxy group at the 2-position (1a) was more favorable for cytotoxic activity than a hydrogen atom (1b).

Anti-inflammatory activities of furanoditerpenoids and other constituents from Fibraurea tinctoria.

Five new furanoditerpenoids, epi-8-hydroxycolumbin (1), fibaruretin B (2), C (3), E (5), and F (6), were isolated from the stems of Fibraurea tinctoria, as well as fibaruretin D (4) from the natural source for the first time, and 39 known compounds. The structures (1-6) were elucidated on the basis of spectroscopic analysis. All the isolated furanoditerpenoids (1-16) were examined for their in vitro activity and some were in vivo anti-inflammatory activity. Compounds 8 and 9 showed significant anti-inflammatory action administered at a dose of 100mg/kg of reducing carrageenan mice paw edema, whereas compound 7, 9, 10, 14, and 16 were more potent to inhibit NO production. The inhibitory effects of these compounds are dose-dependent (1-4 microg/ml).

New diterpenoids and the bioactivity of Erythrophleum fordii.

A phytochemical investigation of the leaves of Erythrophleum fordii Oliv. has led to the isolation of three new cassaine-type diterpenoids, erythrofordin A (1), erythrofordin B (2) and erythrofordin C (3), as well as a norcassaine diterpenoid with a novel skeleton, norerythrofordin A (4), and 27 known compounds (5-31). The structures of 1-4 were elucidated on the basis of spectroscopic analysis. Selected compounds from this plant were examined for anti-inflammatory activity. Taraxerol (16) displayed potent NO-reducing activity in microglial cells, and gallic acid (27) exhibited excellent DPPH radical-scavenging effects.

Cytotoxic phenanthroindolizidine alkaloids from the roots of Ficus septica.

Activity-monitored fractionation of the CHCl3 solubles of the MeOH extract of the roots of Ficus septica using cytotoxicity assay led to the isolation of twenty phenanthroindolizidine alkaloids, including ten new ficuseptines E-N and ten known compounds. The cytotoxic effects of some of the isolates were tested on gastric adenocarcinoma (NUGC) and nasopharyngeal carcinoma (HONE-1) cell lines and the results demonstrated that, with the exception of dehydrotylophorine, all the tested compounds displayed pronounced cytotoxic activity with significant cell growth inhibitory effects. In addition, 13a R-antofine was found to be highly effective with ED(50) values of < 0.1 microg/mL against L-1210, P-388, A-549 and HCT-8 cell lines in another assay.

Anti-inflammatory, anticholinesterase and antioxidative constituents from the roots and the leaves of Salvia nipponica Miq. var. formosana

Reactive oxygen species and granule proteases produced by neutrophils contribute to the pathogenesis of inflammatory diseases. The extracts of the roots and the leaves of Salvia nipponica var. formosana were showed potent inhibitory effects on superoxide anion production in fMLP/CB-activated human neutrophils as well as other anti-inflammatory effects, and led to the isolation of 25 compounds. Among them, compounds 8, 12, 13, 14, 15, 17 and 20 were exhibited more potent inhibitory effect on superoxide anion generation and elastase release by human neutrophils in response to fMLP/CB. Moreover, those isolated compounds also showed significant anticholinesterase and antioxidative activities. To the best of our knowledge, this is the first report of phytochemical and biological activity study on S. nipponica var. formosana.

Constituents of leaves of Phellodendron chinense var. glabriusculum

The leaves of Phellodendron chinense var. glabriusculum yielded three new flavanones, phellodensin D (1), phellodensin E (2), and phellodensin F (3) along with five known compounds, amurensin (4), phellamurin (5), methyl caffeate (6), beta-sitosterol (7), and pheophytin-a (8). The structural assignment of new compounds was based on spectroscopic studies.

Eurycomalin A, a New Dimeric Dihydrobenzofuran from Eurycoma longifolia

One new dimeric 2-isopropenyl-2, 3-dihydrobenzofuran, eurycomalin A (1), was characterized from the methanol extract of the root of Eurycoma longifolia by the 1D and 2D spectral and chemical transformation studies. The reported structure of eurycomalide A (2) was revised through detail 2D spectral analyses.