{"title":"Theoretical Prediction of the Phenoxyl Radical Formation Capacity and Cyclooxygenase Inhibition Relationships by Phenolic Compounds","authors":"J. Ruiz, R. Pouplana","doi":"10.1002/QSAR.200290003","DOIUrl":null,"url":null,"abstract":"Due to the importance of the O-H bond dissociation in the antioxidant mechanism of anti-inflammatory phenols, we studied the biradical process Ph-OH → PhO . +H . for 25 phenolic compounds using ah initio calculations. Enthalpies of reaction (ΔH r ), changes in the electron density at the O-H bond critical point (ρ O H ) and total atomic charges of ortho and para carbon atoms strongly correlate with the in vitro inhibition of cyclooxygenase activity by phenols. The most active compounds have large values of the electron density at the O-H bond (ρ O H ), thus favouring the O-H bond dissociation. In contrast, inactive compounds have small values of the electron density at the O-H bond (ρ O H ), thus reducing the hydrogen donation ability. These results are also supported by the representation of the molecular electrostatic potentials maps. The prediction of the cyclooxygenase inhibitory activity of the proposed QSAR equations is analysed using the multilineal (MLR) method. Finally, the differences in biological activity are examined by analysing the binding interactions of active compounds in the pocket site of human COX-2 enzyme structure derived from crystallographic X -ray data.","PeriodicalId":20818,"journal":{"name":"Quantitative Structure-activity Relationships","volume":"422 1","pages":"605-612"},"PeriodicalIF":0.0000,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"9","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Quantitative Structure-activity Relationships","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/QSAR.200290003","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 9
Abstract
Due to the importance of the O-H bond dissociation in the antioxidant mechanism of anti-inflammatory phenols, we studied the biradical process Ph-OH → PhO . +H . for 25 phenolic compounds using ah initio calculations. Enthalpies of reaction (ΔH r ), changes in the electron density at the O-H bond critical point (ρ O H ) and total atomic charges of ortho and para carbon atoms strongly correlate with the in vitro inhibition of cyclooxygenase activity by phenols. The most active compounds have large values of the electron density at the O-H bond (ρ O H ), thus favouring the O-H bond dissociation. In contrast, inactive compounds have small values of the electron density at the O-H bond (ρ O H ), thus reducing the hydrogen donation ability. These results are also supported by the representation of the molecular electrostatic potentials maps. The prediction of the cyclooxygenase inhibitory activity of the proposed QSAR equations is analysed using the multilineal (MLR) method. Finally, the differences in biological activity are examined by analysing the binding interactions of active compounds in the pocket site of human COX-2 enzyme structure derived from crystallographic X -ray data.
鉴于O-H键解离在抗炎酚类化合物抗氧化机制中的重要作用,我们研究了Ph-OH→PhO的双自由基过程。+ H。25种酚类化合物使用从头计算。反应焓(ΔH r)、O-H键临界点的电子密度变化(ρ O H)和邻位碳原子和对位碳原子的总电荷与酚类物质对环加氧酶活性的体外抑制密切相关。最活跃的化合物在O-H键处具有较大的电子密度(ρ O H),因此有利于O-H键的解离。相反,非活性化合物在O-H键上的电子密度(ρ O H)值较小,从而降低了给氢能力。这些结果也得到了分子静电势图的支持。利用多线性(MLR)方法对所建立的QSAR方程的环加氧酶抑制活性进行了预测。最后,通过晶体X射线数据分析人类COX-2酶结构口袋部位活性化合物的结合相互作用,研究了生物活性的差异。