Aims and Objectives: The aim of this study was to derive robust and reliable QSAR
models for clarification and prediction of antioxidant activity of 43 heterocyclic and Schiff bases
dipicolinic acid derivatives. According to the best obtained QSAR model, structures of new compounds
with possible great activities should be proposed.
Methods: Molecular descriptors were calculated by DRAGON and ADMEWORKS from optimized
molecular structure and two algorithms were used for creating the training and test sets in both set of
descriptors. Regression analysis and validation of models were performed using QSARINS.
Results: The model with best internal validation result was obtained by DRAGON descriptors
(MATS4m, EEig03d, BELm4, Mor10p), split by ranking method (R2 = 0.805; R2
ext = 0.833; F =
30.914). The model with best external validation result was obtained by ADMEWORKS descriptors
(NDB, MATS5p, MDEN33, TPSA), split by random method (R2 = 0.692; R2
ext = 0.848; F = 16.818).
Conclusion: Important structural requirements for great antioxidant activity are: low number of
double bonds in molecules; absence of tertial nitrogen atoms; higher number of hydrogen bond
donors; enhanced molecular polarity; and symmetrical moiety. Two new compounds with potentially
great antioxidant activities were proposed.