Pharmacophore-based virtual screening of catechol-o-methyltransferase (COMT) inhibitors to combat Alzheimer's disease.
Pharmacophore-based virtual screening of catechol-o-methyltransferase (COMT) inhibitors to combat Alzheimer's disease.
复制标题
DOI：
10.1080/07391102.2017.1404931
复制
发表时间：
2018-11
影响因子：
4.4
通讯作者：
Pandya HA
中科院分区：
文献类型：
--
作者：
Patel CN;Georrge JJ;Modi KM;Narechania MB;Patel DP;Gonzalez FJ;Pandya HA
阿尔茨海默病（Alzheimer's disease，AD）是最重要的神经退行性疾病之一，其症状多见于老年人。儿茶酚邻甲基转移酶（COMT）是已知的负责AD的靶酶之一。使用23种已知的COMT抑制剂，通过对1500个诱饵的数据库进行筛选以获得GH评分和富集值，生成并验证了查询。在线ZINC Pharmer对已知抑制剂的关键特征进行了评估，以从ZINC数据库中识别新的线索。从ZINC Pharmer中检索到500个匹配结果，并通过使用FAF-Drug-3进行ADMET（吸收、分布、代谢、排泄和毒性）过滤，考虑将36个分子用于分子对接。从COMT抑制剂中选择了奥匹卡朋、非诺多泮和槲皮素，而选择ZINC 63625100_413、ZINC 39411941_412、ZINC 63234426_254、ZINC 63637968_451和ZINC 64019452_303进行具有高结合亲和力和结构识别的分子动力学模拟分析。本研究通过基于药效团的抑制剂筛选确定了潜在的COMT抑制剂，从而更全面地了解分子水平的相互作用。
Alzheimer’s disease (AD) is one of the most significant neurodegenerative disorders and its symptoms mostly appear in aged people. Catechol-o-methyltransferase (COMT) is one of the known target enzymes responsible for AD. With the use of 23 known inhibitors of COMT, a query has been generated and validated by screening against the database of 1500 decoys to obtain the GH score and enrichment value. The crucial features of the known inhibitors were evaluated by the online ZINC Pharmer to identify new leads from a ZINC database. Five hundred hits were retrieved from ZINC Pharmer and by ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtering by using FAF-Drug-3 and 36 molecules were considered for molecular docking. From the COMT inhibitors, opicapone, fenoldopam, and quercetin were selected, while ZINC63625100_413 ZINC39411941_412, ZINC63234426_254, ZINC63637968_451, and ZINC64019452_303 were chosen for the molecular dynamics simulation analysis having high binding affinity and structural recognition. This study identified the potential COMT inhibitors through pharmacophore-based inhibitor screening leading to a more complete understanding of molecular-level interactions.
登录
查看更多内容
影响因子：
3
作者：
Krieger E;Vriend G
通讯作者：
Vriend G
影响因子：
2.9
作者：
Jatana, Nidhi;Sharma, Aditya;Latha, N.
通讯作者：
Latha, N.
影响因子：
2.9
作者：
Lemkul, Justin A.;Bevan, David R.
通讯作者：
Bevan, David R.
影响因子：
3.7
作者：
Das P;Kang SG;Temple S;Belfort G
通讯作者：
Belfort G
影响因子：
5.6
作者：
Keasar, C;Levitt, M
通讯作者：
Levitt, M