Insights into activity enhancement of 4-aminoquinoline-based hybrids using atom-based and field-based QSAR studies

Malaria has remained one of the most devastating diseases, and the problem has further complicated due to wide spread of chloroquine (CQ)-resistance strain of Plasmodium falciparum. In order to overcome this problem, efforts are being made to develop new chemical entities that can solve the problem of drug resistance. In this context, both atom-based and field-based 3D-QSAR (3-Dimensional quantitative structure–activity relationship) studies were carried out for some of our recently reported 4-aminoquinoline hybrids. The four models generated have shown good correlation coefficients r (0.97, 0.97, 0.94, and 0.95) and test set prediction coefficients q (0.86, 0.88, 0.93, and 0.89). The 3D-QSAR models gave insights into the facts about the changes in the activity pattern with the change in pyrimidine, triazine, and triazole rings. These models will be useful in the future projects of developing new antimalarial compounds against both the CQ-sensitive and CQ-resistance strains of P. falciparum.