فهرست مطالب aicha laoud

Tuberculosis (TB) is one of the top ten causes of mortality worldwide, necessitating the discovery of new molecules with potential anti-tuberculosis activity. In this study, Pretomanid derivatives as potent anti-TB agents were collected from the literature to generate a 3D-QSAR model and conduct molecular docking. The 3D-QSAR model was successfully generated with a high regression coefficient R²= 0.98 and an excellent cross-validated determination coefficient Q2cv= 0.51 for the training set. Furthermore, the model developed showed good predictive ability, with a high predictive value Q2= 0.75 for the test set. The generated 3D contour cubes were applied to find the structural properties necessary to inhibit Deazaflavin-dependent nitroreductase. Then, the results were used to discover novel molecules with a potential anti-tuberculosis activity using the structure-based virtual screening. Based on successful results obtained by virtual screening, twelve compounds were selected as potential inhibitors of the Ddn with highly predicted activities, binding interactions, and acceptable ADME properties.

A virtual screening protocol, by combining on 3D-QSAR model with molecular docking procedure and prediction of physico-chemical properties, was applied to find novel inhibitors of Enoyl ACP reductase against M. tuberculosis. Initially, a series of thirty two isoniazid analogues was collected from literature and was investigated against tuberculosis target (PDB Id: 2IE0) using molecular docking. The docking studies were used to position the inhibitors into the active site of Enoly ACP reductase to derive a receptor based 3D-QSAR model. 3D-QSAR model was built and showed to be statistically significant and with a high predictive ability for the training (R2= 0.97) and test set (Q2= 0.73). Contour cubes analysis of the 3D-QSAR model revealed the chemical features necessary for the enoyl ACP reductase enzyme inhibition. The model was then used for virtual screening with the aim of identifying new inhibitors of Enoyl ACP reductase and predicts their potential activity. The outcome of the above studies, ten new molecules are proposed as Enoyl ACP reductase inhibitors with high binding affinity, activity prediction and favorable ADME properties.