Virtual Conference
Pharma Conference 2022

Nathalie Moussa

Damascus University, Syria

Title: Pharmacophore model Docking, QSAR and Molecular Dynamics Simulation studies of substituted cyclic imides and herbal medicines as COX-2 inhibitors


Cyclooxygenase-2 (COX-2) enzyme inhibitors have not eliminated the necessity for developed drugs not only in the nonsteroidal anti-inflammatory drug (NSAIDs) area but also in other therapeutic applications, including prevention of cancer and Alzheimer disease. A series of novel substituted cyclic imides has been reported as selective COX-2 inhibitors. In order to understand the structural features responsible for their activity, a 3D validated pharmacophore and quantitative structure?activity relationship (QSAR) model have been developed. The values of EF, GH, AUC, sensitivity and specificity refer to the good ability of the pharmacophore model to identify active compounds. Multiple linear regression (MLR) produced statistically significant QSAR model with (R2 training = 0.763, R2test = 0.96) and predictability (Q2training = 0.66, Q2test = 0.84). Then, using the pharmacophore and QSAR models, nine authenticated botanicals, existed in two herbal medicines, and ZINC compounds database were virtually screened for ligands to COX-2. The retrieved hits which also obey of lipinski’s roles of five (RO5) were docked in COX-2 3D structure to investigate their binding mode and affinity. Finally, on the basis of docking results, nine molecules were prioritized as promising hits that could be used as leads to discover novel COX-2 inhibitors. COX-2 inhibition of most of these hits has not been reported previously. Our utilization of 3D pharmacophore model, QSAR, and molecular docking trials can be a potent strategy to successfully predict activity, efficiently design drugs and screen large numbers of new compounds as active drug candidates.


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