Prediction and evaluation of the lipase inhibitory activities of tea polyphenols with 3D-QSAR models.
Prediction and evaluation of the lipase inhibitory activities of tea polyphenols with 3D-QSAR models.
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利用3D-QSAR模型预测和评价茶多酚的脂肪酶抑制活性
DOI：
10.1038/srep34387
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发表时间：
2016-10-03
影响因子：
4.6
通讯作者：
He RR
中科院分区：
文献类型：
--
作者：
Li YF;Chang YQ;Deng J;Li WX;Jian J;Gao JS;Wan X;Gao H;Kurihara H;Sun PH;He RR
茶叶中多酚类化合物具有显著的降血脂作用，这在我们以前的研究中已经得到证实。为了获得活性更强的化合物，利用分子对接得到的活性最强化合物的构象，建立了具有良好预测能力的胰脂肪酶抑制剂3D-QSAR模型，并通过CoMFA和CoMISA方法进行了验证。在CoMFA中具有良好的统计学意义（r2cv= 0.622，r2= 0.956，F = 261.463，SEE = 0.096）和CoMISA（r2 cv = 0.631，r2 = 0.932，F = 75.408，SEE = 0.212）模型，我们总结了结构-多酚类化合物与胰脂肪酶抑制活性之间的活性关系，并发现R2、R4和R5中的大取代基，R1中的亲水性取代基和R2中的吸电子基团是提高脂肪酶抑制活性的关键因素。在3D-QSAR研究结果的指导下，利用多酚氧化酶粗品催化EGCG氧化聚合，得到了一种有效的脂肪酶抑制剂（2 R，3R，2′R，3′R）-去没食子酰Longtheanin-3，3 ′-O-digallate（DOTD），其IC 50为0.08 μg/ml。DOTD还能抑制橄榄油负荷大鼠的脂质吸收，其机制可能与抑制肠粘膜及内容物中脂肪酶活性有关。
The extraordinary hypolipidemic effects of polyphenolic compounds from tea have been confirmed in our previous study. To gain compounds with more potent activities, using the conformations of the most active compound revealed by molecular docking, a 3D-QSAR pancreatic lipase inhibitor model with good predictive ability was established and validated by CoMFA and CoMISA methods. With good statistical significance in CoMFA (r2cv= 0.622, r2= 0.956, F = 261.463, SEE = 0.096) and CoMISA (r2cv= 0.631,r2= 0.932, F = 75.408, SEE = 0.212) model, we summarized the structure-activity relationship between polyphenolic compounds and pancreatic lipase inhibitory activities and find the bulky substituents in R2, R4and R5, hydrophilic substituents in R1and electron withdrawing groups in R2are the key factors to enhance the lipase inhibitory activities. Under the guidance of the 3D-QSAR results, (2R,3R,2′R,3′R)-desgalloyloolongtheanin-3,3′-O-digallate (DOTD), a potent lipase inhibitor with an IC50 of 0.08 μg/ml, was obtained from EGCG oxidative polymerization catalyzed by crude polyphenol oxidase. Furthermore, DOTD was found to inhibit lipid absorption in olive oil-loaded rats, which was related with inhibiting the activities of lipase in the intestinal mucosa and contents.
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影响因子：
7.3
作者：
CHO, SJ;TROPSHA, A
通讯作者：
TROPSHA, A
影响因子：
2.9
作者：
Muthas, Daniel;Sabnis, Yogesh A.;Karlen, Anders
通讯作者：
Karlen, Anders
影响因子：
3.8
作者：
Afantitis, Antreas;Melagraki, Georgia;Igglessi-Markopoulou, Olga
通讯作者：
Igglessi-Markopoulou, Olga
DOI：
10.1107/s0907444902015391
发表时间：
2002-11-01
影响因子：
2.2
作者：
Potterton, E;McNicholas, S;Noble, M
通讯作者：
Noble, M
影响因子：
4.2
作者：
Crespy, V;Williamson, G
通讯作者：
Williamson, G