Application of Hansch's model to guaianolide ester derivatives: a quantitative structure-activity relationship study.
A quantitative structure-activity study to evaluate the effect of lipophilia/aqueous solubility on etiolated wheat coleoptiles elongation has been carried out with 34 guaianolides having different numbers of hydroxyl 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 microM. Data show a strong influence of lipophilia, expressed as logP values. Specially, data from alkylic side 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 reliance is provided. Moreover, all active compounds fit the Lipinski's rule of five. Also, the presence of additional hydroxyl groups and their derivatives in the basic skeleton does not affect the mode of action but greatly 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 derivatives by increasing differences in van der Waals interactions.
Macías
Francisco A
FA
Grupo de Alelopatía, Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Cádiz, c/ República Saharaui s/n, Apdo. 40, 11510 Puerto Real, Cádiz, Spain. famacias@uca.es
Velasco
Raúl F
RF
Castellano
Diego
D
Galindo
Juan C G
JC
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004952:Esters / Q000737:chemistry*; D006900:Hydroxylation; D008433:Mathematics; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D045789:Sesquiterpenes, Guaiane / Q000737:chemistry* / Q000494:pharmacology*; D012995:Solubility; D014908:Triticum / Q000187:drug effects; D014867:Water
D004952:Esters; D045789:Sesquiterpenes, Guaiane; D014867:Water