3D-QSAR Studies, Molecular Docking and Adme Property Prediction of Mannosyl Triazoles Used as Potent Antiadhesives of Uropathogenic E. coli

Abstract

Urinary tract infections (UTIs) are among the most common infectious diseases, accounting for almost five million cases annually and causing considerable morbidity and mortality. Escherichia coli is a commensal inhabitant of the mammalian large intestine and the most common cause of UTIs in humans. Increasing incidence of antibiotic-resistant E. coli causing up to 95% of these infections, calls for additional therapeutic considerations. In this study, 3D-quantitative structure-activity relationship (3D-QSAR) analysis using kNN-MFA method was performed on a series of mannosyl triazoles derivatives as FimH antagonists and discovered four potent novel FimH antagonists. Here, inhibitory concentration, IC₅₀ for 26 antagonists were used, which were already approved for clinical treatment, and the best model was evaluated using random selection method by division of dataset into training and test set. The stepwise forward-backward kNN-MFA methodology was used for model building. The selected best 3D-QSAR model has training set of 23 molecules and test set of three molecules. Significant values of the cross-validated correlation q² (0.76) and predictive correlation coefficient pre_r² (0.88) revealed that this model have reasonable power to predict the biological affinity of new compound in interactions with lectin FimH receptor. The drug likeness of these molecules was checked through ADMET property prediction.

Keywords: uropathogenic Escherichia coli (UPEC), urinary tract infections (UTIs), bacterial adhesin FimH, FimH antagonists, kNN-MFA

Cite this Article

Ansari S, Misra BN, Srivastava V. 3D-QSAR Studies, Molecular Docking and Adme Property Prediction of Mannosyl Triazoles Used as Potent Antiadhesives of Uropathogenic E. coli. Research & Reviews: A Journal of Biotechnology. 2016; 6(1): 26–33p.