Thiazinoquinones Derivatives as Antimalarial Agents: 3D-QSAR Studies, Molecular Docking and Molecular Dynamics Simulations

Abstract

Malaria due to the plasmodium falciparum parasite is one of the major threats to millions of people worldwide, which is usually transmitted to humans by the bite of female anopheles mosquitoes. For this reason, the design of new chemotherapeutic drugs against this parasite infection is important; with this idea, a series of Thiazinoquinones have been used to generate 3D-QSAR models, and molecular docking was performed. In addition, Molecular Dynamics simulations confirmed the stability of the selected complex systems during 2 ns using GROMACS. Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methods were used to construct predictive 3D-QSAR models using the PLS method. The result shows high values of R2=0.96; Q2=0.81; R2pred=0.91 and R2= 0.97; Q2= 0.88; R2pred= 0.81 for CoMFA and CoMSIA models, respectively. The molecular docking results showed that the most active molecules have two hydrogen bonds with Ser 111, this type of bond is absent in the case of the less active molecule. To measure the stability, flexibility, and average distance between the target and compounds, root means square deviations (RMSD), root means square fluctuation (RMSF), and radius of gyration (Rg) was calculated and showed a good result.