Quantitative structure activity relationship and molecular docking of antimalarial tricyclic 1,2,4-trioxane derivatives

Abstract

A set of 32 antimalarial tricyclic 1,2,4-trioxane compounds was subjected to classical QSAR, 3D-QSAR(CoMFA) and molecular docking studied. All compounds were geometry optimized with ab-initio method at the HF/3-21G level. The activities measured against NF54 strain of malarial parasites were used. The models obtained from classical QSAR and 3D-QSAR(CoMFA) techniques are satisfied based on both statistical significance and predictive ability. For docking studies, The atomic charges of these compounds were obtained from single point calculations using 6-31G(d) basis set and the atomic charges of heme were calculated at 6-311G(d,p) level. The results derived from the structure-based design using molecular docking study reveal that Fe Fe[superscript 2+] approaches tricyclic 1,2,4-trioxane compounds at the O[subscript 1] or O[subscript 2] atoms depending on the substituted position of the compound. These results suggested similar mechanism of action to that of artemisinin. All results can support each other and can be used as a guideline to design and predict the new compounds with increasing malarial inhibitory activities.