Application of Hansch's Model to Guaianolide Ester Derivatives: A Quantitative Structure-Activity Relationship Study
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- 作者：Francisco A. Mací ; as ; Raú ; l F. Velasco ; Diego Castellano ; and Juan C. G. Galindo
- 刊名：Journal of Agricultural and Food Chemistry
- 出版年：2005
- 出版时间：May 4, 2005
- 年：2005
- 卷：53
- 期：9
- 页码：3530 - 3539
- 全文大小：429K
- 年卷期：v.53,no.9(May 4, 2005)
- ISSN：1520-5118
文摘
A quantitative structure-activity study to evaluate the effect of lipophilia/aqueous solubility on etiolatedwheat coleoptiles elongation has been carried out with 34 guaianolides having different numbers ofhydroxyl groups and ester side chains of variable length and structure: linear, branched, aromatic,and unsaturated. Compounds have been tested in a range of concentrations between 10 and 1000
M. Data show a strong influence of lipophilia, expressed as logP values. Specially, data from alkylicside chain ester derivatives adjust to the mathematical model based on Hansch's transport theory;hence, a quantitative structure-activity relationships (QSAR) correlation with a high degree of relianceis provided. Moreover, all active compounds fit the Lipinski's rule of five. Also, the presence of additionalhydroxyl groups and their derivatives in the basic skeleton does not affect the mode of action butgreatly influences the activity, as they modify the transport through membranes and aqueous phases.Finally, a second hydroxyl group enhances differences of activity between alkylic side chain derivativesby increasing differences in van der Waals interactions.Keywords: Guaianolide; sesquiterpene lactones; acyl derivatives; isozaluzanin C; 5
chars/alpha.gif" BORDER=0>-hydroxyisozaluzanin C; wheat etiolated coleoptile; QSAR; Hansch's transport model; Lipinski's rule of five; logP;lipophilia; aqueous solubility; membranes
M. Data show a strong influence of lipophilia, expressed as logP values. Specially, data from alkylicside chain ester derivatives adjust to the mathematical model based on Hansch's transport theory;hence, a quantitative structure-activity relationships (QSAR) correlation with a high degree of relianceis provided. Moreover, all active compounds fit the Lipinski's rule of five. Also, the presence of additionalhydroxyl groups and their derivatives in the basic skeleton does not affect the mode of action butgreatly influences the activity, as they modify the transport through membranes and aqueous phases.Finally, a second hydroxyl group enhances differences of activity between alkylic side chain derivativesby increasing differences in van der Waals interactions.Keywords: Guaianolide; sesquiterpene lactones; acyl derivatives; isozaluzanin C; 5chars/alpha.gif" BORDER=0>-hydroxyisozaluzanin C; wheat etiolated coleoptile; QSAR; Hansch's transport model; Lipinski's rule of five; logP;lipophilia; aqueous solubility; membranes