Development predictive QSAR models for artemisinin analogues by various feature selection methods: a comparative...

Quantitative structure-activity relationship (QSAR) models were derived for 179 analogues of artemisinin, a potent antimalarial agent. The activities of these compounds were investigated by means of multiple linear regression (MLR). To select relevant descriptors, several methods including stepwise selection, successive projection algorithm and an ant colony optimization algorithm (called memorized_ACS) were employed. A wide variety of molecular descriptors belonging to various structural properties were calculated for each molecule. Two matrixes (D1 and D2) of molecular properties were built. The D1 matrix included the calculated descriptors and the D2 matrix contained the first to third orders of the calculated descriptors and the logarithm of absolute values of the calculated descriptors. For both data matrixes, significant QSAR models were obtained by the memorized_ACS algorithm. The reactive and PEOE (partial equalization of orbital electronegativity) descriptors represented the highest impact on the antimalarial activity. The PEOE descriptors belong to partial charge descriptors and the reactive descriptor is an indicator of the presence of the reactive groups in the molecule. The best MLR model has a training error of 0.71 log RA units (r (2 )= 0.81) and a prediction error of 0.48 log RA units (r (2) = 0.88).