Insight into the Structural Requirements of Protoporphyrino- gen Oxidase Inhibitors： Molecular Docking and CoMFA of Di- phenyl Ether, Isoxazole Phenyl, and Pyrazole Phenyl Ether
Insight into the Structural Requirements of Protoporphyrino- gen Oxidase Inhibitors： Molecular Docking and CoMFA of Di- phenyl Ether, Isoxazole Phenyl, and Pyrazole Phenyl Ether作者机构：Key Laboratory of Pesticide & Chemical Biology Ministry of Education College of Chemistry Central China Normal University Wuhan Hubei 430079 China USDA/ARS Natural Products Utilization Research Unit P.O. Box 8048 University MS 38677 USA Department of Crop Sciences University of lllinois Urbana IL 61801 USA
出 版 物：《Chinese Journal of Chemistry》 (中国化学（英文版）)
年 卷 期：2013年第31卷第9期
页 面：1153-1158页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 090403[农学-农药学(可授农学、理学学位）] 100705[医学-微生物与生化药学] 09[农学] 0904[农学-植物保护] 0703[理学-化学] 10[医学]
主 题：protoporphyrinogen oxidase Quantitative Structure-Activity Relationship (QSAR) Comparative Mo-lecular Field Analysis (CoMFA) diphenyl ether isoxazole phenyl pyrazole phenyl ether
摘 要：Protoporphyrinogen oxidase （PPO, EC 1.***.3.4） is one of the most significant targets for a large family of in- hibitors that may be used as herbicide, bactericide, fungicide, or photosensitizing activator to treat cancer through photodynamic therapy （PDT）. Molecular docking and CoMFA were combined in a multistep framework with the ultimate goal of identifying important factor contributing to the activity of PPO inhibitors. As a continuation of the previous research work on the development of new PPO inhibitors, the bioassay results indicated that good PPO in- hibitors were discovered in all of the three chemical series with ICs0 values ranging from 0.010 to 0.061 pmol·L ^-1. Using the crystal structure of tobacco mitochondrial PPO （mtPPO） as template, all the compounds were docked into the enzyme active site. The docking pose of each compound was subsequently used in a receptor-based alignment, leading to the development of a significant CoMFA model with r^2 value of 0.98 and q^2 （cross validation r^2） value of 0.63. This novel multistep framework gives insight into the and it can be extended to other classes of PPO inhibitors. In be particularly applicable in virtual screening procedures. structural characteristics for the binding of inhibitors, addition, the simplicity of the proposed approach may
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