Molecular docking and 3D-QSAR studies of falcipain inhibitors using CoMFA, CoMSIA, and Open3DQSAR

3D-QSAR and docking studies of 124 falcipain inhibitors, 2-pyrimidinecarbonitrile derivatives as antimalarial drugs have been carried out. Most descriptive components method was used for dividing the compounds into training (94 compounds) and test (30 compounds) sets. The CoMFA and CoMSIA give cross-validated rcv2 and non-cross-validated rncv2 correlation coefficients as 0.616 and 0.446, and 0.918 and 0.801, respectively. The Open3DQSAR was used as free available software to process the molecular interaction fields (MIFs) generated by CoMFA and CoMSIA of SYBYL 7.3. The models generated by Open3DQSAR on CoMFA and CoMSIA MIFs give rcv2 values of 0.810 and 0.586 and rncv2 of 0.921 and 0.823, respectively. The external validation indicated that Open3DQSAR models using CoMFA and CoMSIA MIFs possess good predictive power with rpred2 values of 0.946 and 0.662, respectively. Molecular docking was employed to explore the binding mode between these compounds and the receptor, as well as help understanding the structure–activity relationship revealed by CoMFA and CoMSIA.