• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1995년도 춘계학술대회
• /
• pp.66-66
• /
• 1995

Mutated forms of the ras oncogenes are associated with about 30% of human tumors. The ras genes encode 21KDa proteins, called p21 or Ras, that are associated with the plasma membrane. FPTase is a dimeric enzyme that catalyses the transfer of the farnesyl group from farnesyl pyrophosphate onto cysteine 186 at the C-terminus of the Ras protein. This is mandatory process for triggering ras oncogene toward tumor formation. Therefore, selective inhibitors of FPTase have the potential to be used as antitumorgenic agents.

• Applied Biological Chemistry
• /
• 제51권4호
• /
• pp.309-315
• /
• 2008

돌단풍 지상부를 80% MeOH로 추출하고, 얻어진 추출물을 EtOAc, n-BuOH 및 $H_2O$로 용매 분획하였다. 이 중 EtOAc 및 n-BuOH 분획으로부터 silica gel chromatography를 반복하여 5개의 화합물을 분리하였다. 각 화합물의 화학구조는 NMR, MS 및 IR 등의 스펙트럼 데이터를 해석하여, astragalin (1), kaempferol 3-O-${\alpha}$-L-rhamnopyranosyl (1${\rightarrow}$6)-${\beta}$-D-glucopyranoside (2), rutin(3), kaempferol 3-O-${\alpha}$-L-rhamnopyranosyl(1${\rightarrow}$4)-${\alpha}$-Lrhamnopyranosyl(1${\rightarrow}$6)-${\beta}$-D-glucopyranoside(4), quercetin 3-O-${\alpha}$-L-rhamnopyranosyl(1${\rightarrow}$4)-${\alpha}$-L-rhamnopyranosyl(1${\rightarrow}$6)-${\beta}$-Dglucopyranoside(5)로 동정하였다. 이들 화합물은 FPTase 활성을 억제하였으며, 특히 화합물 3(rutin)은 rat H-ras 세포주의 생장과 bFGF로 유도시킨 HUVECs의 cell migration을 억제하는 것으로 나타났다.

• Applied Biological Chemistry
• /
• 제42권1호
• /
• pp.68-72
• /
• 1999

비스 방향족 ${\alpha},{\beta}$-불포화 케톤 유도체들중 비교적 양호한 farnesyl protein transferase(FPTase) 저해활성을 나타낸 1,3-diphenylpropenone 유도체들에 대하여 in vitro에서 사람의 종양세포주인 A549(폐암)를 비롯하여 SKMEL-2(피부암), HCT-15(결장암), SKOV-3(자궁암) 및 XF-498(뇌암)등 5종의 종양 세포주에 대한 세포독성을 측정하고 기질분자의 치환기 변화에 따른 구조-활성관계(SAR)를 Free-Wilson방법과 Hansch방법으로 검토하였다. 전체적으로 styryl group중의 Y-치환기보다 benzoyl group중의 X-치환기가 세포독성에 큰 영향(X>Y)을 미쳤으며, 2,4-dichloro 치환체, 15와 2,4-dimethyl 치환체, 16이 모든 종양 세포주에 대하여 가장 높은 세포독성을 나타내었다. 또한, X-치환기는 주로 적정값$({\sigma}_{opt}=0.22{\sim}0.29})$의 약한 전자끌게$({\sigma}>0)$에 의한 전자전달 효과$({\sigma})$에 의존적으로 세포독성이 증가하는 반면에 Y-치환기는 logP, $B_1$ 및 R상수 등 다양한 요소로 영향을 미치고 있음을 알았다.

• 한국작물학회:학술대회논문집
• /
• 한국작물학회 2006년도 한국약용작물학회 공동춘계학술발표회
• /
• pp.522-523
• /
• 2006

• 한국약용작물학회지
• /
• 제15권2호
• /
• pp.82-88
• /
• 2007

From the EtOAc fraction of Eugenia caryophyllata, four compounds were isolated through activity-guided silica gel column chromatography, From the result of spectroscopic data including NMR, MS and IR, the chemical structures of the compounds were determined as 1-allyl-4-hydroxy-3-methoxybezene acetate (eugenol acetate, 1), 1-allyl-4-hydroxy-3-methoxybezene (eugenol, 2), $3{\beta}-hydroxyolean-12-en-28-oic$ acid (oleanolic acid, 3) and $2{\alpha}$, $3{\beta}-dihydroxyolean-12-en-28-oic$ acid (maslinic acid, 4). Compounds 3 and 4 were isolated for the first time from this plant. Also, compounds 1, 2 and 3 exhibited relatively high platelet aggregation inhibitory activity with the $IC_{50}$ values of 0.24, 0.09 and 0.07 mM, respectively. Compound 2 significantly prolonged activated partial thromboplastin time (aPTT) with the value of $124{\pm}11.2$ seconds as compared to the control with the value of $37.5{\pm}2.2$ seconds at the concentration of 50 ${\mu}g/ml$. Compounds 1 and 3 revealed inhibitory activity on farnesyl protein transferase (FPTase) with the $IC_{50}$ values of 0.49 and 0.24 mM and compounds 1 and 2 highly inhibited the growth of rat-H-ras cells with the $Gl_{50}$ values of 6.63 and 5.70 ${\mu}M$, respectively.

• 한국환경과학회지
• /
• 제28권11호
• /
• pp.993-1004
• /
• 2019

Chrysanthemum boreale Makino (C. boreale) is widely distributed in Asian countries, and has traditionally been used to treat various inflammatory diseases including bronchitis. In this study, we aimed to isolate biologically active compounds from leaves and stems of C. boreale. Chemical components were purified by column chromatograpy and recyclic HPLC, and characterized from their spectral data (IR, MS, NMR). Biological activity experiments were conducted for Farnesyl-protein transferase (FPTase) activity, apoptosis and nitirc oxide (NO) release. As a results, three sesquiterpene lactones were isolated. Compound 1 (4-methoxy-8-O-acetyl-10-hydroxy-2,11(13)-guaiadiene-12,6-olide) showed strong cytotoxic activities having an average growth inhibition of 50% ($GI_{50}$) value of $1.89{\mu}g/m{\ell}$ against human colon adenocarcinoma cells. Compound 1 also showed a low half maximal inhibitory concentration ($IC_{50}$) value of $10{\mu}g/m{\ell}$ for NO release. In the caspase 3 activity, compound 1 and compound 2 (8-O-(2-carbonyl-2-butyl)-3,10-dihydroxy-4,11(13) -guaiadiene-12,6-olide) exhibited 94% and 90% apoptosis inhibition activity, respectively. Compound 3 (4,8-O-diacetyl -10-hydroxy-2(3),11(13)-guaiadiene-12,6-olide) showed a strong inhibitory effect on FPTase activity with 90% inhibitory activity at a concentration of $100{\mu}g/m{\ell}$. These results clearly show the presence of lactone compounds in the leaves and stems, which may partially contribute to the pharmacological activity of C. boreale.

• Journal of Applied Biological Chemistry
• /
• 제51권2호
• /
• pp.66-68
• /
• 2008

• Applied Biological Chemistry
• /
• 제51권4호
• /
• pp.334-337
• /
• 2008

• BMB Reports
• /
• 제30권4호
• /
• pp.280-284
• /
• 1997

Phenylglyoxal diethyl pyrocarbonate (DEPC), and 1-cyclohexyl-3-[2-morpholinoethyl]-carbodiimide metho-p-toluenesulfonate (CMC) are modifying reagents specific for arginine, histidine, and aspartate or glutamate, respectively. They were found to inactivate S. cerevisiae farnesyl protein transferase (FPTase). The peptide substrate protected the enzyme against inactivation by CMC and the other substrate farnesyl pyrophosphate showed protection against inactivation by phenylglyoxal. while neither of the two substrates protected the enzyme against DEPC inactivation. These results suggest the presence of aspartate/glutamate, arginine and histidine residues at the active site of this enzyme.

• Journal of Applied Biological Chemistry
• /
• 제50권4호
• /
• pp.249-253
• /
• 2007

Thirteen edible plants previously reported to show inhibitory activities on farnesyl protein transferase (FPTase) and phosphatase of the regenerating liver-3 (PRL-3) were evaluated for inhibitory activity on the proliferation of human umbilical vein endothelial cells (HUVECs). Four plant extracts, Oenothera erythrosepala, Perilla frutescens, Panicum miliaceum, and Quercus acutissima, significantly inhibited the proliferation of HUVECs induced by the basic fibroblast growth factor (bFGF) without cytotoxicity at 100 ${\mu}g/mL$. Myristica fragrans, Rosmarinus officinalis, and Syringa patula also showed inhibitory activity on the proliferation with only mild cytotoxicity.