3D-QSAR, ADME-Tox, and molecular docking of semisynthetic triterpene derivatives as antibacterial and insecticide agents

• Published in: Structural chemistry 2022, Vol.33 (4), p.1063-1084
• Main Authors: Daoui, Ossama, Mazoir, Noureddine, Bakhouch, Mohamed, Salah, Mohammed, Benharref, Ahmed, Gonzalez-Coloma, Azucena, Elkhattabi, Souad, Yazidi, Mohamed El, Chtita, Samir
• Format: Article
• Language: English
• Subjects: Analysis; Antibacterial agents; Chemistry; Chemistry and Materials Science; Computer Applications in Chemistry; Insecticides; Latex; Molecular docking; Original Research; Physical Chemistry; Proteins; Receptors; Theoretical and Computational Chemistry; Three dimensional models
• ISSN: 1040-0400; 1572-9001
• DOI: 10.1007/s11224-022-01912-4

In the present work, 27 triterpene derivatives have been subjected to 3D-QSAR, ADME-Tox, and molecular docking for their insecticidal activity. The selected derivatives are previously semi-synthesized based on compounds obtained from Euphorbia resinifera and Euphorbia officinarum latex. The in silico studies were used to predict and to evaluate the antibacterial and insecticidal properties of the 3D structure of triterpene derivatives. The 3D-QSAR models are developed using CoMFA and CoMSIA techniques, and they have showed excellent statistical results ( R 2  = 0.99; Q 2  = 0.672; R 2 pred  = 0.91 for CoMFA and R 2  = 0.97; Q 2  = 0.61; R 2 pred  = 0.94 for CoMSIA). The results indicate that the built models are able to describe the relationship between the structure of triterpene derivatives and the pLD 50 bioactivity. Based on contour maps obtained from CoMFA and CoMSIA models, 38 new molecules are designed and their pLD 50 activities are predicted. The drug-like and ADME-Tox properties of the molecule designed are examined and led to the selection of four molecules ( 55 , 56 , 59 , 64) as promising antibacterial and insecticidal agents. Compounds 55 , 56 , 59 , and 64 are able to inhibit the MurE (PDB code: 1E8C) and EcR (PDB code: 1R20) proteins involved in the process of antibacterial and insecticidal activities. This hypothesis is confirmed by the implementation of a molecular docking test. This test predicted the most important referential interactions that occur between the structure of triterpene derivatives and the targeted receptors. Among the four docked molecules, three molecules ( 55 , 56 , and 59) showed greater stability than the reference molecule 16 inside the MurE and EcR receptors pocket. Therefore, the structure of the three new triterpene derivatives can be adopted as reference for the synthesis of antibacterial drugs and also in the development of insecticides.