• Applied Biological Chemistry
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• v.43 no.2
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• pp.95-99
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• 2000

A series of hetero ring (X) substitued chalcone derivatives with farnesyl protein transferase (FPTase) inhibition activities $(pI_{50})$ values determined in vitro is analyzed by modified Free-Wilson (F-W) and Hansch method for quantitative structure activity relationship (QSARs). On the basis of F-W analysis on the FPTase inhibitory activity of a training set of the compounds, none of the (X)-substituents were not contribute the activity. But the net charge of ${\alpha}$ carbon atom is contribute the activity than that of ${\beta}$ carbon atom. And the relative orders of the (Y)-substituents on the activity are ortho>meta>para-substituents. According to Hansch approach, the activities would depend largely on the optimal, $(R_{opt.}=-0.35)$ resonance effect with ortho substituted $(I_o>0)$ electron donating group (R<0) and STERIMOL parameter, $B_1$ constant. The inhibition activity between hetro ring substituents have been a proportioned with each others and none substituent(H), 45 showed the highest FPTase inhibition $(pI_{50}=4.30)$ activity.

• Applied Biological Chemistry
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• v.45 no.4
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• pp.223-227
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• 2002

Characteristic stereostructures of farnesyl protein transferase (FPTase) inhibition materials isolated from Artemisia sylvatica and regioselectivity of biogenic Diels-Alder reactions between dehydromatricarin molecules A and B were examined quantitatively. Results revealed that the major reaction of frontier molecular orbital (FMO) interaction proceeds through charge-control reaction between LUMO of A16, dienophile and HOMO of B1, diene, and the isolated 8-acetylarteminolide and artanomaloide were minor products. FPTase inhibition activity and hydrophobicity of 8-acetylarteminolide were $pI_{50}=3.75$ and logP=2.62, respectively. FPTase inhibition activity of 8-acetylarteminolide was higher than those of artanomaloide and dehydromatricarin.

• Applied Biological Chemistry
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• v.42 no.3
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• pp.252-255
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• 1999

Inhibition activities$(pI_{50})$ of chalcone derivatives as substrate with farnesyl protein transferase(FPTase) were determined in vitro. The structure activity relationships(SAR) between the activity and physicochemical parameters of X & Y-substituents on the phenyl groups were analyzed by Free-Wilson and Hansch method. X-substituents on the benzoyl group have the more important role to inhibition activity than Y-substituents on the styryl group. Among them, none substituent, 8 showed the highest FPTase inhibition activity$(pI_{50}=4.30)$. Particularly, the SAR equation could be formulated, showing a parabolic relationship between the activity and hydrophobicity(logP) where the optimal value$({\Sigma}logP)_{opt}$ was 3.915. And also the activity depends on the steric effect(Es > 0) with X-substituent and the resonance effect(R < 0) with electron donating Y-substituents. Based on the results of SAR analyses, the interactions between substrates and receptor, FPTase, could be assumed.

• Korean Journal of Pharmacognosy
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• v.30 no.1
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• pp.70-73
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• 1999

Nine sesquiterpene lactones, which were isolated from Hemisteptia lyrata Bunge. Chrysanthemum zawadskii Herbich var. latilobum Kitamura and Chrysanthemum boreale Makino were evaluated for the farnesyl-protein transferase (FPTase) inhibitor, conducted by the scintillation proximity assay (SPA). The angeloylcumambrin B and tigloylcumambrin B inhibited a recombinant rat FPTase with $IC_{50}$ value of $78\;{\mu}g/ml$ $(225\;{\mu}M)$ and $90\;{\mu}g/ml$ $(260 \;{\mu}M)$, respectively.

• Journal of Ginseng Research
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• v.25 no.4
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• pp.156-161
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• 2001

We investigated the effects of polyacetylenes of ginseng on farnesyl protein transferase (FPTase) and carboxyl methyl transferase (CMTase) activities related to post-translational modification of Ras protein. We also investigated the effect of petroleum ether extract (PEE) of ginseng on progression of cell cycle. FPTase activity was respectively inhibited 16.2% by 10mM panaxynol and 21.3% by 10mM panaxydol, whereas CMTase activity was not inhibited by panaxynol or panaxydol. Treatment of PEE significantly reduced the numbers and size of human colon cancer cell (HT-29) and human liver cancer cell(HepG2) cultured, respectively. To investigate the mechanism of growth inhibition by PEE of ginseng, we analyzed the cell cycle progressions of PT-29 and HepG2 cells, respectively. We found that PEE significantly inhibited progression of cell cycle from G1 to S phase. These results suggest that anticancer effects of PEE were derived from the arrest of G1 phase in cell cycle progression.

• Applied Biological Chemistry
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• v.47 no.3
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• pp.357-360
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• 2004

The flower of Campsis granudiflora K. Schum. was extracted with 80% aqueous MeOH, and the concentrated extract was partitioned with EtOAc, n-BuOH and $H_2O$. From the EtOAc fraction, four compounds were isolated through the repeated silica gel and ODS column chromatographies. From the result of physico-chemical data including NMR, MS and IR, the chemical structures of the compounds were determined as linolenic acid methyl ester, linoleic acid methyl ester, ${\beta}-sitosterol$ and daucosterol. Daucosterol inhibited FPTase activity with $IC_{50}$ values of $14{\pm}0.04\;{\mu}M$.

• Journal of Applied Biological Chemistry
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• v.52 no.4
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• pp.221-225
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• 2009

Lithospermum erythrorhizon has been known well as one of traditional medicine for fever reduction, detoxication, and blood circulation improvement. This study was carried out to isolate biological active compounds from roots of Lithospermum erythrorhizon and to investigate their low density lipoprotein (LDL) antioxidant and anticancer activities. The hexane extract of Lithospermi Radix has been separated on silica gel chromatography and a naphthoquinone pigment compound 1 has been isolated. The structure of the compound 1 has been identified by spectroscopic technique, including MS and NMR, as acetylshikonin (1). Acetylshikonin showed significantly inhibitory activity on $Cu^{2+}$-induced human LDL oxidation with $IC_{50}$ value of $8.8\;{\mu}M$ and obvious anticancer effect by inhibiting farnesyl:protein transferase (FPTase) activity with $IC_{50}$ value of $23\;{\mu}M$, which suggested that acetylshikonin might be useful for the treatment of atherosclerosis and cancer.

• Korean Journal of Pharmacognosy
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• v.34 no.1 s.132
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• pp.91-99
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• 2003

Ras proteins play an important role in intracellular signal transduction pathways involved in cell growth and the mutated twas genes have been found in thirty percent of human cancers. Ras proteins (H-, K- and N-Ras) are small guanine nucleotide binding proteins that undergo a series of posttranslational modifications including the farnesylation onto cysteine 186 at C-terminal of Ras by farnesyl protein transferase (FPTase). This is a mandatory process for retention of transforming ability. Therefore, inhibitors of FPTase have a promising to be effective antitumor agents. In our screening program for FPTase inhibitors, the methanol extracts of 193 plants were screened for the inhibitory activity against FPTase partially purified from the rat brain. Extracts of 7species plants including Areca catechu, Saururus chinensis, Curcuma longa, Artemisa princeps, Paeonia suffruticosa, Spatholobus suberectus, Cinnamomum cassia, Cinnamomum japonicum inhibited more than 60% of FPTase activity at a concentration of $100\;{\mu}g/ml$.

• Applied Biological Chemistry
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• v.47 no.2
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• pp.251-257
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• 2004

The root of lxeris dentata forma albiflora was extracted with 80% aqueous MeOH and solvent fractionated with EtOAc, n-BuOH and water, successively. From the EtOAc and n-BuOH fractions, four sesquiterpene compounds were isolated through the repeated silica gel and ODS column chromatographies. The chemical structures were determined as zaluzanin C (1), $9{\alpha}-hydroxyguaian-4(l5),10(14),11(13)-triene-6,12-olide$ (2), $3{\beta}-O-{\beta}-D-glucopyranosyl-8{\alpha}-hydroxyguaian-4(15),10(14 )-diene-6,12-olide$ (3), and $3{\beta}-O-{\beta}- D-glucopyranosyl-8{\beta}hydroxyguaian-10(14)-ene-6,12-olide$ (4) through the interpretation of several spectral data including 2D-NMR. Some showed the inhibitory effects on DGAT (Diacylglycerol acyltransferase), ($IC_{50}$ values of 1, 2: 0.13, 0.10 mM), the catalyzing enzymes of the intracellular esterification of diacylglycerol and FPTase (Famesyl-protein transferase), ($IC_{50}$ values of 1, 2: 0.15, 0.18 mM), the farnesylation enzyme for Ras protein charge of cancer promotion.

• Applied Biological Chemistry
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• v.42 no.1
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• pp.68-72
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• 1999

The cytotoxicity of 1,3-diphenylpropenone derivatives known to inhibit the farnesyl protein transferase (FPTase) was examined against various established tumor cell line, A549 (lung cancer), SKMEL-2 (uterine cancer), HCT-15 (skin cancer), SKOV-3 (brain cancer) and XF-498 (colon cancer) of the 1,3-diphenylpropenone derivatives showing farnesyl protein transferase (FPTase) inhibition activity. And the structure-activity relationship (SAR) between structure of 1,3-diphenylpropenone derivatives as substrate and cytotoxicity was investigated by Free-Wilson analysis as well as Hansch method with tumor cell lines. From the result of Free-Wilson analyses, X-substituents on the benzoyl group have a more important role than Y-substituents on the styryl group. The 2,4-dichloro substituent, 15 and 2,4-dimethyl substituent, 16 showed the highest cytotoxicity (average pI_(50)=5.0). Particulary, the cytotoxicity of X-substituents increased with electronic effect $({\sigma})$ due to weak electron withdrawing group with optimum value $({\sigma}_{opt}=0.22{\sim}0.29})$ whereas that of Y-substituent resulted from various factors such as logP, $B_1$ and R constant.