QSAR study on the antimalarial activity of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors

Plasmodium falciparum, the most fatal parasite that causes malaria, is responsible for over one million deaths per year. P. falciparum dihydroorotate dehydrogenase (PfDHODH) has been validated as a promising drug development target for antimalarial therapy since it catalyzes the rate-limiting step for DNA and RNA biosynthesis. In this study, we investigated the quantitative structure–activity relationships (QSAR) of the antimalarial activity of PfDHODH inhibitors by generating four computational models using a multilinear regression (MLR) and a support vector machine (SVM) based on a dataset of 255 PfDHODH inhibitors. All the models display good prediction quality with a leave-one-out q2 >0.66, a correlation coefficient (r) >0.85 on both training sets and test sets, and a mean square error (MSE)