Aim: QSAR techniques and docking increase the probability of success and reduce time and coast\nin drug discovery process. The study presents QSAR investigation on 20 pyrimidine derivatives for\nantitubercular activity against M. tuberculosis.\nMaterials and Methods: The relationship analysis between compounds and physicochemical\nproperties under study was done by two methods Multiple linear regression (MLR) and Step wise\nSelection of Terms (SW). The results show good models with six and five (SW) parameters linear\nequations. While the molecular docking simulation study of selected target Cytochrome P450\n14alpha-sterol demethylases (CYP51) of M. tuberculosis H37Rv(1E9X) and ligands (active\npyrimidine derivatives) as well as 4-Phenyl-1h-Imidazol for comparison was performed by using\nAutodock software.\nResults: The best model predicted in this study was the eq. 1 (MLR) with excellent statistical fit as\nSE = 9.06234 R-Sq = 94.9% R-Sq (adj) = 92.1% and F=34.107, while the best model by (SW)\nwas the eq. 2 with excellent statistical fit as SE= 8.89630 R-sq= 94.64% R-sq (adj)= 92.40% F=42.354. All the parameters showed insignificant role in the antitubercular activity. The molecular\ndocking of ligands 3a-j with the cytochrome P450 14alpha-sterol demethylases (CYP51) of\nM. tuberculosis H37Rv was examined and the best docked pose was shown to have one hydrogen\nbond with PRO386. While the compound 4-Phenyl-1h-Imidazolshowed lower scores of docker\nenergy.\nConclusion: Quantum chemical calculated parameters can be successfully used in the derived a\ndesigner QSAR. And the study indicated that predicted antitubercular activity values for pyrimidine\nderivative compounds can be modeled by two methods; stepwise (SW) and multiple linear\nregression (MLR), as well as the docking analysis showed that all compounds exhibited quite\nsimilar binding energy and compound 4 as best ligand which showed the highest binding energy\nand this agreement with experimental data. The most compounds understudy exhibit the best\nresults comparison with the ligand 4-Phenyl-1h-Imidazol.All the rustles could potentially offer a\nnew opportunity in the design of novel properties or extended to other compounds.
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