Quantitative structure-activity relationship of organosulphur compounds as soybean 15-lipoxygenase inhibitors using CoMFA and CoMSIA.
Three-dimensional quantitative structure-activity relationship studies were carried out on a series of 28 organosulphur compounds as 15-lipoxygenase inhibitors using comparative molecular field analysis and comparative molecular similarity indices analysis. Quantitative information on structure-activity relationships is provided for further rational development and direction of selective synthesis. All models were carried out over a training set including 22 compounds. The best comparative molecular field analysis model only included steric field and had a good Q² = 0.789. Comparative molecular similarity indices analysis overcame the comparative molecular field analysis results: the best comparative molecular similarity indices analysis model also only included steric field and had a Q² = 0.894. In addition, this model predicted adequately the compounds contained in the test set. Furthermore, plots of steric comparative molecular similarity indices analysis field allowed conclusions to be drawn for the choice of suitable inhibitors. In this sense, our model should prove useful in future 15-lipoxygenase inhibitor design studies.
Centro de Bioinformática y Simulación Molecular, Facultad de Ingeniería en Bioinformática, Universidad de Talca, 2 Norte 685, Casilla 721, Talca, Chile. jmcr77@yahoo.com
Julio
J
Caballero
Michael
M
Fernández
Deysma
D
Coll
D001093:Arachidonate 15-Lipoxygenase / Q000737:chemistry; D003198:Computer Simulation; D020128:Inhibitory Concentration 50; D008024:Ligands; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008956:Models, Chemical; D008958:Models, Molecular; D009930:Organic Chemicals / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D013025:Glycine max / Q000737:chemistry*; D013455:Sulfur / Q000737:chemistry / Q000494:pharmacology
D008024:Ligands; D016859:Lipoxygenase Inhibitors; D009930:Organic Chemicals; D013455:Sulfur; D001093:Arachidonate 15-Lipoxygenase