In silico study of 2,4,5-trisubstituted thiazoles as inhibitors of tuberculosis using 3D-QSAR, molecular docking, and ADMET analysis

Authors : Ayoub KHALDAN, Soukaina BOUAMRANE, Reda EL-MERNİSSİ, Hamid MAGHAT, Mohammed Aziz AJANA, Abdelouahid SBAİ, Mohammed BOUACHRINE, Tahar LAKHLIFI

Pages : 452-468

Doi:10.31202/ecjse.961940

View : 12 | Download : 7

Publication Date : 2022-05-31

Article Type : Research Paper

Abstract :In order to discover new efficient drug used as inhibitor of tuberculosis, three-dimensional quantitative structure-activity relationship insert ignore into journalissuearticles values(3D-QSAR); was executed on set of eighteen 2,4,5-trisubstituted thiazoles compounds. CoMFA and CoMSIA models were molded using 14 molecules as training set. They give a significant coefficient of R2 insert ignore into journalissuearticles values(0.995 and 0.982 respectively); and important values of Q2 insert ignore into journalissuearticles values(0.533 and 0.601, respectively);. The robust of these models was checked by an external validation using a test set of 4 molecules, affords significant R2test values of 0.654 and 0.648 for CoMFA and CoMSIA models, respectively. CoMFA and CoMSIA contour maps provided much valuable information to identify the main regions impacting insert ignore into journalissuearticles values(decreasing or increasing); the antituberculosis activity. These outcomes guided us to design new entities with important activities. Molecular docking was put into effect to guess the types and modes of interactions between 2,4,5-trisubstituted thiazoles molecules and receptor insert ignore into journalissuearticles values(PDB: 4ZDJ);. In silico ADMET analysis was executed to measure the pharmacokinetic properties of newly designed molecules.
Keywords : Molecular docking, 3D QSAR, anti tuberculosis, thiazoles, ADMET