Jong Woong Ahn

Antitumor activity of some phenolic components in plants

The activity-guided fractionation of some medicinal plants led to yield five kinds of natural stilbene compounds namely 3,5-dihydroxy-4′-methoxystillbene(I), rhapontigenin(II), resveratrol (III), rhaponticin(IV) and piceid(V) and two common flavonoids, apigenin(VI) and luteolin(VII) as active principles of the antitumor property, in vitro, against five kinds of human tumor cell lines, A-549, SK-OV-3, SK-MEL-2, XF-498 and HCT15.

Apicidin, a histone deacetylase inhibitor, induces differentiation of HL-60 cells

The fungal metabolite apicidin (cyclo(N-O-methyl-L-tryptophanyl-L-isoleucinyl-D-pipecolinyl-L-2-amino-8-oxodecanoyl)) inhibited the growth of HL-60 cells in a concentration-dependent manner (100-1000 nM). At higher concentrations (>300 nM), cell death was induced. At 100 nM, it induced hyperacetylation of histone H4 time-dependently, while trichostatin A induced transient hyperacetylation. Apicidin (10-100 nM) increased the cells having nitroblue tetrazolium-reducing activity and expressing CD11b but not CD14 and CD15. The expression of CD11b by apicidin was long lasting, while that by trichostatin A was transient. In K562 cells, apicidin at 10-100 nM did not inhibit cell growth nor express CD11b, CD14 and CD15. Our findings indicate that apicidin inhibits proliferation and induces the early stage of differentiation of HL-60 cells.

Antitumor triterpenes from medicinal plants

Thirteen kinds of naturally occurring or derivatised triterpenes, reported to have an antitumoral property, were reinvestigated on the basis of their direct cytotoxicity or the inhibitory activity on cell growth against five kinds of cultured human tumor cells,i. e., A-549, SK-OV-3, SK-MEL-2, XF498 and HCT15,in vitro. Ursonic acidIII, betulinic acidVIII, betulonic acidX and glycyrrhetinic acidXI were exhibited a marked inhibition on cell growth.

In vitro antitumour activity of flavonoids from Sophora flavescens

The cytotoxicity‐guided fractionation of the roots of Sophora flavescens (Leguminosae) extracts led to the isolation of 15 active principles 1–15, responsible for cytotoxicity against five kinds of cultured human tumour cell lines, i.e. A549 (non small cell lung), SK‐OV‐3 (ovary), SK‐MEL‐2 (skin), XF498 (central nerve system) and HCT‐15 (colon), evaluated by SRB method in vitro. Compounds 2–14 were classified as unusual flavonoids occurring exclusively in this species and the proliferation of each of the examined tumour cells were significantly inhibited during continuous exposure to compounds 1–15 for 48u2009h, respectively.

Antiviral activity of triterpenoid derivatives

Abstract3-Oxo or/and 11-oxo derivatives of natural 3-hydroxy triterpenes,i.e., 3-oxoursolic acidIa, 11-oxoursolic acidIb, 3,11-dioxoursolic acidIc, 3-oxobetulinic acidIIa and 3-oxopomolic acidVIa were exhibited to show an increased anti-HSV-1 activityin vitro, four to ten times as much as corresponding parent 3-hydroxy compounds.

Induction of apoptosis of RAW 264.7 cells by the cytostatic macrolide apicularen A

In RAW 264.7 cells, a mouse leukaemic monocyte cell line, apicularen A decreased cell growth and survival as assessed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay in a concentration‐dependent manner at 10–1000 nM. Apicularen B, an N‐acetyl‐glucosamine glycoside of apicularen A, was 10–100‐fold less effective than apicularen A. Apicularen A induced a DNA ladder, an increase in the percentage of sub‐G1 cells and annexin V‐binding cells, and promoted the activation of caspase as revealed by the cleavage of poly(ADP‐ribose) polymerase, indicating that apicularen A induced apoptosis in RAW 264.7 cells. In addition, apicularen A phosphorylated p44/42 mitogen‐activated protein kinase (MAPK) and p38 MAPK. The p44/42 MAPK inhibitor PD98059 rescued the cells from apicularen‐induced decrease in cell growth and survival as determined by the MTT assay, while the p38 MAPK inhibitor SB203580 augmented the effect of apicularen A. This suggested the activation of p44/42 MAPK to be pro‐apoptotic and the activation of p38 MAPK anti‐apoptotic in apicularen A‐treated RAW 264.7 cells.

Antitumor activity ofTrichosanthes kirilowii

The activity-directed fractionation upon the MeOH extract of the root ofTrichosanthes kirilowii led to the isolation of eight cucurbitane triterpenes namely cucurbitacin B (I), isocucurbitacin B (II), cucurbitacin D (III), isocucurbitacin D (IV), 3-epi-isocucurbitacin B (V), dihydrocucurbitacin B (VI), dihydroisocucurbitacin B (VII) and dihydrocucurbitacin E (VIII), as active principles. All isolates were shown to exhibit significant cytotoxicity against cultured human tumor cells, including A-549, SK-OV-3, SK-MEL-2, XF-498 and HCT 15, with an exceptionally high potency.

The structure of kushenol M fromSophora flavescens

The linkage pattem of two side chainsi.e., a isopentenyl and a lavandulyl group in kushenol M(I), a flavonoid fromSophora flavescens was established by the aid of 2-D NMR techniques, especially DEPT,13C−1H COSY and COLOC experiments. Thus,I was unequivocally determined as (2R,3R)-5,7,2′,4′-tetrahydroxy-6-isopentenyl-8-lavandulylflavanonol.

Immunomodulating activities of water extract fromXanthium strumarium (II): Immunostimulating effects of the water layer after treated with chloroform

One of water and/or methanol extracts from 14 herbal drugs which were screened using murine splenocytes showed immunosuppressive activities previously. After water extract fromXanthium strumarium was treated with chloroform, 100μg/ml of water layer (XS-WC1) has very strong immunostimulating activities tested by3H-thymidine incorporation (control vs 100μg/ml, 4962 cpm vs 69515 cpm). MLR also appears to be stimulated strongly (control vs 100μg/ml, 26345 cpm vs 78688 cpm). When 100μg/ml of XS-WC1 and 0.8μg/ml of concanavalin A (ConA) were added, more3H-thymidine were incorporated significantly, compared with 0.8μg/ml of ConA only. In contrast with ConA, results from 5μg/ml of lipopolysaccharide (LPS) and 100μg/ml of XS-WC1 were not different, compared with 5μg/ml of LPS only. These results indicated that responses of XS-WC1 to B cell and T cell may be different. XS-WC1 was injected intraperitoneally (10mg/kg, 50mg/kg, 100mg/kg) for 4 days or 10 days and tested secretion of IgM or IgG by direct and indirect hemolytic plaque-forming cell assays, respectively. Numbers of hemolytic plaques for both IgM and IgG were increased significantly. Especially, secretion of IgGs was increased more than 10 times. After administration of XS-WC1 for 7 days (50mg/kg, 100mg/kg) splenomegaly due to graft vs host reaction was observed. Human lymphocytes separated from whole blood by Ficoll-Hypaque method were also proliferated after treatment of 10μg/ml and 50μg/ml of XS-WC1. As seen in murine lymphocytes, human lymphocyte proliferation was increased synergistically after treatment with both of XS-WC1 and phytohemagglutinin (PHA). It appears that XS-WC1 may have potential immunostimulating activities and that it remains to be purified further for isolation of active components.

5′-O-TBDMS-3′-O--(1H-Imidazole-1-Thiocarbonyl)thymidine: A Novel Intermediate for the Synthesis of 2,3′-Anhydrothymidine

Abstract Thermal or base-promoted conversion of 5′-O-TBDMS-3′-O-(1H-imidazole-1-thiocarbonyl)thymidine (1) afforded 5′-O-TBDMS-2,3′-anhydro-thymidine (2), a pivotal intermediate for the transformation of the 3′-hydroxy group of 2′-deoxyribonucleosides, in high yield.