• 생약학회지
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• 제37권3호
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• pp.206-211
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• 2006

The methanol extract from seed of Myristica fragrans (Myristicaceae) demonstrated a potent inhibition on the pro-liferation of cultured human tumor cells such as A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCT-15 (colon) in vitro. By the continuous effort to purify the active components responsible far the anti-proliferative effect on tumor cell lines, we have isolated eleven kinds of lignan components, i. e., safrole (1), machilin A (2), licarin B (3), macelignan (4), mere-dihydroguaiaretic acid (5), mγnstargenol A (6), methoxyeugenol (7), machilin F (8), licarin A (9), nectandrin B (10), and 2-(4-allyl-2,6-dimethoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)propan-1-ol (11) together with a novel furan fatty acid, (E)-3-(3-methyl-5-pentylfuran-2-yl) acrylic acid (12) from seed extract of M. fragrans. Chemical structures of the isolated components (1-12) were established bγ the aid of NMR spectroscopic analyses, i. e., COSY HMQC and HMBC. Each of the Isolates demonstrated a potent inhibition on the proliferation of cultured human tumor cells such as A549 (non small cell lung), SK-OY-3 (ovary), SK-MEL-2 (melanoma) and HCT-15 (colon) in vitro.

• 생약학회지
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• 제36권3호통권142호
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• pp.201-204
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• 2005

The rhizome extract of Atractylodes japonica Koidzumi(Compositae) exhibited a particular inhibition on the proliferation of cultured human tumor cell lines, in vitro. Thus, the intensive phytichemical investigation of the MeOH extract of Atractylodes japonica have been conducted by the way of activity-guided purification. The repeated column chromatographic separation of the n-hexane soluble part of extract resulted in the isolation of four sesquiterpenes (1-4) and a polyacetylene component (5). Chemical structures of them were identified as atractylon (1), atractylenolide Ⅰ(2), atractylenolide Ⅲ(3), eudesma-4(15),7(11)-dien-8-one (4) and 1,3-diacetyl-atractylodiol (5) by spectroscopic means. Among the isolates, compound 2-4 were shown to give moderate inhibitory effect in a dose dependent manner on the proliferation of cultured human tumor cell lines such as A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCT 15(colon), respectively.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.608-612
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• 2002

The twelve-protostane analogues were synthesized from alisol B 23-acetate and assessed for their in vitro antitumor activity against six different human and murine tumor cell lines. Of the compounds synthesized, 23S-acetoxy-24R(25)-epoxy-11$\beta$,23S-dihydroxyprotost-13(17)-en-3-hy-droxyimine (12) exhibited significant cytotoxic activities against A549, SK-OV3, B16-F10, and HT1080 tumor cells with $ED_{50}/$ values of 10.0, 8.7 ,5.2, and 3.1 ${\mu}g$/ml, respectively. Furthermore, 23S-acetoxy-13(17),24R(25)-diepoxy-11$\beta$-hydroxyprotost-3-one (5), 13(17),24R(25)-diepoxy-11$\beta$, 23S-dihydroxyprotostan-3-one (6), 24R,25-epoxy-11$\beta$,23S-dihydroxyprotost-13(17)-en-3-one (7), and 11$\beta$,23S,24R,25-tetrahydroxyprotost-13(17)-en-3-one (9) showed moderate cytotoxic activities against 816-F10 and HT1080 tumor cells. These results mean that a hydroxyimino group at C-3 position in the protostane-type terpene enhances cytotoxic activity.

• 대한한방종양학회지
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• 제5권1호
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• pp.19-32
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• 1999

To evaluate the antitumor activity and antimetastatic effects of Kamigumgusingihwan(KGSH) studies have ken done. The results were obtained as follows: 1. KGSH extracts exhibited a weak cytotoxicity against A549, SK-OV-3, B16-F10, and SK-MEL-2 cell lines. But exhibited potent cytotoxicity against P388 cell line in a dose-dependent manner. 2. The concentration inhibiting adhesion of A549, to complex extracellular matrix up to below 30% of control was recognized at $10^{-3}g/ml$ of KGSH 3. KGSH extracts showed a weak inhibitoty effect on DNA topo-isomerase I from calf thymus. 4. The T/C% was 137% in KGSH treated group in S-180 bearing ICR mice. 5. In pulmonary colonization assay, a number of colonies in the lungs were decreased significantly in KGSH treated group as compared with control group. 6. In hematological changes in B16-BL6 injected C57BL/6, numbers of WBC were decreased insignificantly in KGSH treated groups, and also those of platelet were increased insignificantly in KGSH treated groups as compared with control. 7. In CAM assay, KGSH extracts inhibited angiogenesis at $15{\mu}g/egg $concentration significantly as compared with control. Taken together these results, it is strongly demonstrated that KGSH significantly suppressed tumor metastasis by blocking cell adhesion to extracellular matrix. Therefore, KGSH is expected to be clinically a potent antimetastatic drug for the prevention and treatment of cancer.

• 생약학회지
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• 제36권3호통권142호
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• pp.240-244
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• 2005

The methanol extract of the seed of Myristica fragrans (myristicaceae) demonstrated a potent inhibition on the proliferation of cultured human tumor cells such as A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2(melanoma), XF498 (central nerve system) and HCT-15(colon). The MeOH extract was fractionated into three portions by serial solvent partition i,e., EtOAc soluble part, BuOH soluble part and remaining water layer. Among them, the EtOAc soluble part of the extract demonstrated a potent inhibition on the proliferation of cultured human tumor cells, Bioassay-guided fractionation of the EtOAc soluble part led to the isolation of six lignan constituents, i.e., safrole(1), machilin A (2), licarin B (3), macelignan (4), mesodihydroguaiaretic acid (5) and myristargenol A (6) as well as a large amount of myristic acid as active ingredients. Structures of the isolated active components (1-6) were established by chemical and spectroscopic means.

• Archives of Pharmacal Research
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• 제26권1호
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• pp.9-14
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• 2003

For probing the importance of planarity of imidazolidinone motif of 4-phenyl-1-(benzenesulfonyl)imidazolidinones 1 for their cytotoxicity, 4-phenyl-2-(benzoyl)[1,2,5]thiadiazolidine-1,1-dioxide (2a), 4-phenyl-2-(p-toluoyl)[1,2,5]thiadiazolidine-1,1-dioxide (2b), 4-phenyl-2-(phenylcarbamoyl)[1,2,5]thiadiazolidine-1,1-dioxide (3a), and 4-phenyl-2-(p-tolylcarbamoyl)[1,2,5]thiadiazolidine-1,1-dioxide (3b) were prepared along with their regioisomers (5a, 5b, 9a, 9b) and their cytotoxicity were measured against human lung carcinoma (A549), human colon carcinoma (COLO205), human ovarian cancer (SK-OV-3), human leukemic cancer (K562), and murine colon adenocarcinoma (Colon26) cell lines in vitro. All compounds prepared do not show any activity against all five cancer cell lines unlike 1. Compounds 1 possess planarity of imidazolidinone, especially in sulfonylurea moiety ($-SO_2$NHCONH-). However compounds 2 and 3 have nonplanar 5-membered ring, [1,2,5]thiadiazolidine-1,1-dioxides. Such structural differentiation might result in the loss of activity. Therefore the inactivity of 2 and 3 could also be an indication for the necessity of planarity of imidazolidinone ring of 1 for their cytotoxic activity.

• Archives of Pharmacal Research
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• 제29권9호
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• pp.721-727
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• 2006

To continue exploration of structure activity relationship of novel 1-(indoline-5-sulfonyl)-4-phenylimidazolidinones (1) reported as anticancer agent with broad spectrum, three 1-(arylsulfonyl)-4-vinylimidazolidinones (2) were synthesized from methyl serinate (3) in 8 steps. Reaction of intermediate 2-phenoxycarbonylaminobut-3-enyl p-toluenesulfonate (10) with arylsulfonamide in the presence of potassium carbonate produced corresponding 2 and N-(4-vinyloxazolidin-2-yl)arylsulfonamide 11 in approximately equal ratio. This reaction is believed to undergo through urea intermediate 16 as shown in scheme 3. 1-Arylsufonyl-4-vinylimidazolidinones 2 show much reduced activity against human colon carcinoma (Colo205), human chronic myelogenous leukemia (K562), and human ovarian adenocarcinoma (SK-OV-3) and compatible activity against human lung carcinoma (A549) compared to 1. Therefore phenyl at 4-position should be the optimum planar motif for the activity of 1.

• 생약학회지
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• 제35권2호통권137호
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• pp.134-138
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• 2004

A bioassay-guided fractionation of the whole extract of Viscum album var. coloratum Ohwi (Loranthaceae) led to the isolation of two triterpenoidal components; oleanolic acid (1) and ${\beta}-amyrin$ acetate (2), and a flavonoid, homoflavoyadorinin B (3) as well as large quantity of free fatty acid mixtures as active ingredients of the extract responsible for the antitumoral property. The EtOAc soluble fraction and BuOH soluble fraction of the extract demonstrated a significant inhibition on the proliferation of cultured human tumor cells such as A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system), and HCT-15 (colon) in vitro, whereas the remaining water soluble fraction exhibited a poor inhibition. The intensive phytochemical investigation of the EtOAc soluble fraction and BuOH soluble fraction of the extract indicated that the oleanolic acid (1) and large amounts of free fatty acid mixtures might be attributed to the in vitro antitumoral property of the whole extract of Viscum album var. coloratum.

• Journal of Microbiology and Biotechnology
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• 제15권4호
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• pp.734-739
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• 2005

Myxobacterium sp. HK1, isolated from Korean soil, degrades cellulose, differentiates to fruiting body, and its 16s rDNA has $95\%$ similarity to Polyangium sp. An anticancer molecule, CDMHK, was identified from culture broth of Myxobacterium sp. HK1, and purified by Diaion HP20, Silica gel, Sephadex LH-20 chromatography, and preparative HPLC using an YMC OSD-A C18 column. The molecular structure and formula were determined to be $C_{l2}H_{l9}N_3O_2$ (M.W 237) by MS spectrometry, 300 MHz $^{1}H\;and\;^{13}C$ NMR. The CDMHK was not active against Escherichia coli, Staphylococcus aureus, and Candida albicans. However, this molecule inhibited the growth of various cancer cell lines. The $ED_{50}$ values of CDMHK were determined to be 0.147, 0.086, 0.18, 0.166, and 0.142 $\mu$g/ml against A549, SK-OV-3, SK-MEL-2, VF498, and HCTl5 cancer cell lines, respectively. In addition, the CDMHK was able to induce apoptosis of the CCRF-CEM cancer cell line, evidenced by DNA fragmentation assay and DAPI staining.

• 생약학회지
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• 제34권4호통권135호
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• pp.308-313
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• 2003

A bioassay-guided fractionation of the stem bark extract of Eucommia ulmoides Oliver (Eucommiaceae) led to the isolation of three iridoid constituents, genipin (1), geniposide (3), geniposidic acid (4) as well as $({\pm})-guaiacylglycerol$ (2) and fatty acid mixtures as active ingredients of the extract responsible for the antitumoral property. The EtOAc soluble part and BuOH soluble part of the extract demonstrated a potent inhibition on the proliferation of cultured human tumor cells such as A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCT-15 (colon) in vitro, whereas the remaining water soluble part exhibited a poor inhibition. The intensive investigation of the EtOAc soluble part and BuOH soluble part of the extract yielded genipin, guaiacylglycerol, geniposide, geniposidic acid and large amounts of fatty acid mixtures as active components.