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IC50 values were obtained for two series of isoindolines derived from α-amino acids over cyclooxygenase 1 and 2 (COX-1 and COX-2). In order to explain the biological activity observed, a structure-activity relationship (SAR) model was achieved for the tested compounds and 19 reference compounds with known selective inhibitory activity, through the correlation of the binding energies calculated from rigid docking of the best conformations into the catalytic sites of COX-1 and COX-2, as well as their molecular descriptors: Log P, molecular weight (MW), volume (V), and solvation energy (Esol) versus their experimental IC50 values by MLR and LS-SVM methods. The model probed whether the COX-1 and COX-2 inhibitory activities of the isoindolines correlate with steric, hydrophobic, and thermodynamic parameters. The correlation values with MLR for COX-1 and COX-2 (r(2)  = 0.4193 and r(2)  = 0.5929) were optimized with LS-SVM until r(2)  = 0.6818 for COX-1 and r(2)  = 0.8985 for COX-2, resulting in a good predictive ability for COX-1 and -2 inhibition with this model. In conclusion, the data suggests that the physicochemical descriptors evaluated have an impact on the inhibitory activity and selectivity of isoindolines over COX-1 and COX-2.

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