• Bulletin of the Korean Chemical Society
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• 제29권5호
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• pp.921-927
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• 2008

Discovery of $\alpha$-glucosidase inhibitors has been actively pursued with the aim to develop therapeutics for the treatment of diabetes and the other carbohydrate mediated diseases. As a method for the discovery of new novel inhibitors of $\alpha$-glucosidase, we have addressed the performance of the computer-aided drug design protocol involving the homology modeling of $\alpha$-glucosidase and the structure-based virtual screening with the two docking tools: FlexX and the automated and improved AutoDock implementing the effects of ligand solvation in the scoring function. The homology modeling of $\alpha$-glucosidase from baker’s yeast provides a high-quality 3-D structure enabling the structure-based inhibitor design. Of the two docking programs under consideration, AutoDock is found to be more accurate than FlexX in terms of scoring putative ligands to the extent of 5-fold enhancement of hit rate in database screening when 1% of database coverage is used as a cutoff. A detailed binding mode analysis of the known inhibitors shows that they can be stabilized in the active site of $\alpha$- glucosidase through the simultaneous establishment of the multiple hydrogen bond and hydrophobic interactions. The present study demonstrates the usefulness of the automated AutoDock program with the improved scoring function as a docking tool for virtual screening of new $\alpha$-glucosidase inhibitors as well as for binding mode analysis to elucidate the activities of known inhibitors.

• 생약학회지
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• 제46권2호
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• pp.105-108
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• 2015

To establish the anti-diabetic(α-glucosidase inhibitory) activity of D. lotus leaf extract, isolate and identify the constituents responsible for the activity. The methanolic extract of leaves was partitioned between water, n-butanol and ethyl acetate. Bio-assay guided fractionation, based on inhibition of ;${\alpha}$-glucosidase, allowed isolation and identification of the active components. Liquid chromatography/mass spectrometry(LC/MS), ¹ H-NMR and ¹³ C-NMR spectra analyses demonstrated that the active compound was myricetin-3-O-;${\alpha}$-L-rhamnoside(1). Compound 1 demonstrated a strong inhibition on the α-glucosidase, in vitro and ;${\alpha}$-glucosidase inhibitory value was calculated as 98.08%, when that of a reference drug, acarbose was estimated as 83.03%. The present study indicates compound 1 could be considered as an ;${\alpha}$-glucosidase inhibitor and developed as an important antidiabetes agent for type II diabetes therapy.

• Applied Biological Chemistry
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• 제48권1호
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• pp.103-108
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• 2005

${\alpha}-Amylase$ 저해제는 소장에서 전분의 소화를 저해하여 포도당의 흡수를 지연시킴으로써 혈당 조절 목적으로 이용된다. 따라서 본 연구에서는 ${\alpha}-amylase$ 저해제를 탐색할 목적으로 국내 자생 목본류 약 1400여종의 70% ethanol 추출액을 대상으로 ${\alpha}-amylase$ 저해제 분포를 검색하였다. 수종의 목본류에서 ${\alpha}-amylase$ 저해제가 분포하고 있음이 확인되었으며, 그 중 활성이 비교적 높은 말채나무 기원의 저해제를 대상으로 연구를 진행하였다. 기원별 효소에 따른 저해 활성도를 살펴보면 salivary와 pancreatic ${\alpha}-amylase$, 미생물 기원의 ${\alpha}-glucosidase$에는 탁월한 저해 활성을 보인 반면 돼지 기원의 ${\alpha}-glucosidase$ 저해제에 대해서는 매우 낮은 저해 활성을 보였다. ${\alpha}-Amylase$와 ${\alpha}-glucosidase$의 kinetic을 분석하면 salivary와 pancreatic 두 효소에 모두 경쟁적 저해제로, 효모의 ${\alpha}-glucosidase$에는 비경쟁적과 반경쟁적의 혼합형 저해제로 나타났다. 또한 열과 산성에 대한 안정성을 확인한 결과 비교적 안정적인 것으로 나타났다. 본 추출물의 식이 섭취에 따른 혈당 강하 효과와 체중에 미치는 영향에서는 혈당과 체중 상승을 억제하는 효과가 확인되었고, mRNA수준에서 대퇴근 세포에 있어서 GLUT4의 발현이 증가됨을 확인하였다.

• Applied Biological Chemistry
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• 제43권1호
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• pp.12-17
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• 2000

Ascorbic acid로부터 $2-O-{\alpha}-D-glucopyranosyl-L-ascorbic$ acid (AA-2G)를 생산하기 위하여, transglucosylation 활성을 가지는 발아미의 ${\alpha}-glucosidase$를 효소원으로 이용하였다. 시험한 6 품종의 벼중에서 일품벼의 ${\alpha}-glucosidase$ 활성이 125.0 unit/ml로 가장 높았으며, 발아후 3일째에서 최대 비활성 8.52 unit/ml protein을 보였다. 일품벼의 조효소액을 이용한 AA-2G 생산에 있어서 glucose 공여체로는 maltose가 가장 좋았으며, maltose와 ascorbic acid의 최적 농도는 각각 125 mM와 175 mM이었다 ${\alpha}-Glucosidase$ 농도는 100 unit에서 가장 좋았으며, 효과적인 완충용액은 sodium citrate였고, 최적 농도는 100 mM이었다 최적 pH 및 반응은도는 각각 5.0과 $60^{\circ}C$이었다. 상기의 최적 반응조건 하에서 35분 반응후에 ascorbic acid로부터 $108.43\;{\mu}M/unit$의 AA-2G가 생산되었으며, 전환율은 ascorbic acid에 대해 6.2%였다.

• 생명과학회지
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• 제27권9호
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• pp.1052-1058
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• 2017

우뭇가사리(Gelidium amansi)는 홍조류로서 우뭇가사리과(Gelidiaceae)에 속한다. 현재까지 우뭇가사리의 항산화 및 항비만 효과 등의 기능들이 연구되었으나 식후 혈당 수치에 미치는 영향에 관한 연구는 부족한 실정이다. 이에 본 연구에서는 Gelidium amansii extract (GAE)가 탄수화물 가수분해 효소(${\alpha}-glucosidase$, ${\alpha}-amylase$)에 미치는 억제 효과 및 streptozotocin (STZ)으로 유도된 당뇨병 마우스의 식후고혈당에 미치는 완화효과를 조사하였다. 정상군과 STZ으로 유도된 당뇨병 마우스에 수용성 전분(2 g/kg body weight)을 경구투여한 후 GAE (300 mg/kg body weight) 또는 acarbose (100 mg/kg body weight)를 단독 또는 함께 투여하였다. 혈당은 꼬리채혈을 통해 0, 30, 60, 120분 간격으로 측정하였다. ${\alpha}-glucosidase$와 ${\alpha}-amylase$에 대한 GAE의 $IC_{50}$ 값은 각각 $0.099{\pm}0.009mg/ml$와 $0.178{\pm}0.038mg/ml$의 결과값을 나타내어, 양성대조군인 acarbose보다 더 효과적이었다. STZ으로 유발된 당뇨병 마우스의 식후 혈당 수치는 대조군에 비해 GAE 투여 시 유의적으로 더 낮았다(p<0.05). 또한 GAE 투여는 당뇨병 마우스에서 포도당 반응에 대한 곡선하면적 감소와 관련이 있었다(p<0.05). 이러한 결과는 GAE가 ${\alpha}-glucosidase$, ${\alpha}-amylas$와 같은 탄수화물 가수분해 효소를 억제함으로써 식후 고혈당을 완화시키는 유용한 천연기능성 식품이 될 것으로 사료된다.

• 한국식품영양과학회지
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• 제31권1호
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• pp.131-135
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• 2002

본 연구에서는 작약 추출물의 식후 과혈당 억제작용을 조사하였다. 작약 유기용매(hexane, ethyl acetate, butanol, water) 추출물들을 high performance liquid chromatogrphy를 이용하여 분획한 분획물(fraction)들으 $\alpha$-glucosidase(EC 3.2.1.20) 저해제를 탐색하였다. 작약 ethyl acetate 추출물의 11, 12, 18, 19번 분획물들은 20 $\mu\textrm{g}$/mL에서 각각 85%, 84%, 77%, 77%의 강력한 저해 활성을 나타내었으며, 작약 ethyl acetate 추출물의 10~19번 분획을 경구투여한 in vivo당 (maltose) 부하 실험에서도 양성대조군과 비교하여 유의성 있게 22%의 혈당을 낮추었다. 따라서 본 연구의 in vitro와 in vivo 실험을 통하여 확인 된 $\alpha$-glucosidase 저해 활성을 갖는 작약 분획물들은 식후의 혈당상승 작용을 억제하는 새로운 nutraceutical 소재와 항당뇨 신약개발을 위한 탐색자원으로서 매우 가치있는 자원으로 기대된다.

• 대한한방내과학회지
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• 제30권3호
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• pp.481-494
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• 2009

Background : Radix Sophora Flavescentis (SF) is used for the treatment of diabetes mellitus in Traditional Korean Medicine. However, little is known about the effects of Radix Sophora Flavescentis extract (SFE) on the hypoglycemic mechanism. Objective : We performed a series of experiments to verify the effects of SFE on the proliferation of RIN-m5F, the secretion and synthetic processes of insulin with glucose stimulation and inhibition of $\alpha$-glucosidase. Methods : Various amounts of SFE were added to the RIN-m5F cell culture to identify the effects on the cell proliferation, total amounts of insulin secretion, and related gene expression at the molecular level. Also to identify the inhibitory effect on the $\alpha$-glucosidase activities, ${\rho}NPG$ assay was done with various SFE concentrations followed by comparison with control. Results : SFE did not show considerable effects on RIN-m5F cells proliferation, insulin secretion or insulin mRNA expression, whichever phenomena did not depend on the glucose concentration. However, SFE significantly inhibited $\alpha$-glucosidase activity in a dose dependent manner compared to control. Conclusions : This study showed that SFE has potent $\alpha$-glucosidase inhibitory activity. Thus, SF may by used for the improvement of overall glycemic control. Further mechanism studies on the lipid toxicity and oxidation stress of SF seem to be necessary.

• 생약학회지
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• 제40권3호
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• pp.229-232
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• 2009

The ethanol (EtOH) extract of the branches of Cotinus coggygria (Anacardiaceae) exhibited a significant inhibition on the yeast $\alpha$-glucosidase, one of the key enzymes related with diabetes mellitus, in a dose dependent manner, in vitro. The intensive phytochemical survey of the EtOH extract of the species by way of bioactivity-guided fractionation resulted in the isolation of 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (1) as an active principle responsible for the inhibition on $\alpha$-glucosidase, together with two related components 2 and 3. Compound 1 demonstrated a strong inhibition on the yeast $\alpha$-glucosidase, in vitro and $IC_{50}$ value was calculated as 0.96 mg/ml, when that of a reference drug, acarbose was estimated as 5.3 mg/ml. On the other hand, other related constituents of the species, 1,2,3,6-tetra-O-galloyl-$\beta$-D-glucose (2) and gallic acid (3) were exhibited relatively poor inhibition upon the yeast $\alpha$-glucosidase, respectively.

• 생약학회지
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• 제40권2호
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• pp.150-154
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• 2009

We examined ethanol extracts prepared from the Korean marine algae belonging to the Sargassaceae family for their inhibitory effects on ${\alpha}$-glucosidase activity and free radicals in vitro. Among five marine algae, the extracts of Sargassum yezoense were found to possess strongly ${\alpha}$-glucosidase inhibition and free radicals scavenging activities. Two compounds were isolated via bioactivity guided isolation and tested for their effects on ${\alpha}$-glucosidase, DPPH, $ABTS^{+}$ and $Photochem^{(R)}$ analysis. Their chemical structures were elucidated by spectral analysis and direct comparison with authentic compounds; their structures were identified as sargaquinoic acid (1) and sargahydroquinoic acid (2). The inhibitory effects of compound 1 and 2 ($IC_{50}$ value:14.2 and 12.8 ${\mu}M$, respectively) on ${\alpha}$-glucosidase were more potent that of deoxynojirimycin as a positive control ($IC_{50}$ value:18.0 ${\mu}M$). All compounds displayed antioxidative activity which was measured by DPPH, $ABTS^{+}$ and $Photochem^{(R)}$ apparatus.

• 약학회지
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• 제55권6호
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• pp.446-450
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• 2011

As an effort to find a new scaffold for ${\alpha}$-glucosidase inhibition, we have prepared total 11 phenylalkylated piperazine derivatives and tested their ${\alpha}$-glucosidase inhibitory activities. Compounds 8 ($IC_{50}=2.73{\pm}0.075mM$) possessing two 3-methoxyphenethyl group on 1,4-position of piperazine showed comparable potency to acarbose used as reference. But other compounds were inactive to ${\alpha}$-glucosidase. The result indicated that proper substituents on the piperazine can engender ${\alpha}$-glucosidase inhibitory activities on the piperazine derivatives.