QSAR and docking studies of 3, 5-dimethylpyrazole as potent inhibitors of Phosphodiesterase-4

Abstract

A quantitative structure-activity relationship (QSAR) study was performed to develop a model on a series of 3, 5-dimethylpyrazole containing furan moiety derivatives which exhibited considerable inhibitory activity against PDE4B. The obtained model has correlation coefficient (r) of 0.934, squared correlation coefficient (r2) of 0.872, and leave-one-out (LOO) cross-validation coefficient (Q2) value of 0.733. The predictive power of the developed model was confirmed by the external validation which has (r2) value of 0.812. These parameters confirm the stability and robustness of the model to predict the activity of a new designed set of 3,5-dimethyl-pyrazole derivatives (I-XV), results indicated that the compound III, V, XIII, and XV showed the strongest inhibition activity (IC50 = 0.2813, 0.5814, 0.6929, 0.6125μM, respectively) against PDE4B compared to the reference rolipram with (IC50=1.9μM). Molecular docking was performed on a new designed compound with PDE4B protein (3o0j). Docking results showed that compounds (X and IX) have high docking affinity of -36.2037 and -33.2888 kcal/mol respectively. Keywords: QSAR, molecular docking, pyrazole derivatives, PDE4 inhibitors, anti-inflammatory.