Heme Oxygenase Database (HemeOxDB) and QSAR Analysis of Isoform1 Inhibitors
Heme Oxygenase Database (HemeOxDB) and QSAR Analysis of Isoform1 Inhibitors
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DOI：
10.1002/cmdc.201700321
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发表时间：
2017-11-22
期刊：
影响因子：
3.4
通讯作者：
Pittala, Valeria
中科院分区：
文献类型：
--
作者：
Amata, Emanuele;Marrazzo, Agostino;Pittala, Valeria
由于对血红素加氧酶（HO）领域的兴趣越来越大，我们建立了一个名为HemeOxDB的配体数据库，其中包括整套已知的HO-1和HO-2抑制剂，产生了400多种化合物。HemeOxDB可在线获得，并且具有强大的搜索引擎，允许最终用户构建复杂的查询，对列表结果进行排序，并生成彩色编码的二维和三维图形。该数据库将成为设计有效和选择性HO-1或HO-2抑制剂的工具。我们也有兴趣在虚拟搜索替代抑制剂，并首次在该领域的HO，定量结构活性关系（QSAR）模型建立使用半最大抑制浓度（IC 50）的值的整套已知HO-1抑制剂，取自HemeOxDB和采用Monte Carlo技术。统计质量表明，该模型是强大的，并具有理想的预测潜力。美国食品和药物管理局（FDA）批准的药物的筛选，在我们的数据集之外，提出了新的预测抑制剂，为取代咪唑基团开辟了道路。本文报道的HemeOxDB和QSAR模型可能有助于前瞻性地鉴定或重新利用具有最佳结构属性的新药物用于HO酶抑制。
Due to increasing interest in the field of heme oxygenases (HOs), we built a ligand database called HemeOxDB that includes the entire set of known HO-1 and HO-2 inhibitors, resulting in more than 400 compounds. The HemeOxDB is available online at , and having a robust search engine allows end users to build complex queries, sort tabulated results, and generate color-coded two- and three-dimensional graphs. This database will grow to be a tool for the design of potent and selective HO-1 or HO-2 inhibitors. We were also interested in virtually searching for alternative inhibitors, and, for the first time in the field of HOs, a quantitative structure-activity relationship (QSAR) model was built using half-maximal inhibitory concentration (IC50) values of the whole set of known HO-1 inhibitors, taken from the HemeOxDB and employing the Monte Carlo technique. The statistical quality suggested that the model is robust and possesses desirable predictive potential. The screening of US Food and Drug Administration (FDA)-approved drugs, external to our dataset, suggested new predicted inhibitors, opening the way for replacing imidazole groups. The HemeOxDB and the QSAR model reported herein may help in prospectively identifying or repurposing new drugs with optimal structural attributes for HO enzyme inhibition.