Three-dimensional QSAR analysis and design of new 1,2,4-oxadiazole antibacterials.
Three-dimensional QSAR analysis and design of new 1,2,4-oxadiazole antibacterials.
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DOI：
10.1016/j.bmcl.2015.12.041
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发表时间：
2016-02-01
影响因子：
2.7
通讯作者：
Mobashery S
中科院分区：
文献类型：
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作者：
Leemans E;Mahasenan KV;Kumarasiri M;Spink E;Ding D;O'Daniel PI;Boudreau MA;Lastochkin E;Testero SA;Yamaguchi T;Lee M;Hesek D;Fisher JF;Chang M;Mobashery S
恶二唑类抗菌药物是一类新发现的对革兰氏阳性菌有活性的化合物，通过抑制青霉素结合蛋白家族的必需酶来靶向细菌细胞壁的生物合成。基于配体的3D-QSAR分析比较分子场分析（CoMFA），比较分子形状指数分析（CoMSIA）和基于场的3D-QSAR评估了一系列的102个成员的这一类。该系列包括无活性化合物以及对金黄色葡萄球菌具有中度至强烈抗菌作用的化合物。使用不同类型的能量最小化和电荷计算构建多个模型。CoMFA导出的等高线图成功地定义了有利的和不利的区域的分子取代的空间和静电性能。
The oxadiazole antibacterials, a class of newly discovered compounds that are active against Gram-positive bacteria, target bacterial cell-wall biosynthesis by inhibition of a family of essential enzymes, the penicillin-binding proteins. Ligand-based 3D-QSAR analyses by comparative molecular field analysis (CoMFA), comparative molecular shape indices analysis (CoMSIA) and Field-Based 3D-QSAR evaluated a series of 102 members of this class. This series included inactive compounds as well as compounds that were moderately to strongly antibacterial against Staphylococcus aureus. Multiple models were constructed using different types of energy minimization and charge calculations. CoMFA derived contour maps successfully defined favored and disfavored regions of the molecules in terms of steric and electrostatic properties for substitution.