A quantitative structure activity relationship (QSAR) model for a series of N-(1-benzyl-3,5-dimethyl-1H-pyrazole-4-yl) benzamide derivatives having autophagy inhibitory activities as potent anticancer agents was developed by the multiple linear regressions (MLR) method. In this study, previous compounds were used in the model development were divided into a set of fifteen compounds as training set and set of four compounds as test set. A model with high prediction ability and high correlation coefficients was obtained. This model showed r = 0.968, r2 = 0.937 and Q2 = 0.880, the QSAR model was also employed to predict the experimental compounds in an external test set, and to predict the activity of a new designed set of 3,5-dimethyl-4-substituted-pyrazole derivatives (1-15), result showed that compound 3 has the most promising inhibition activity (EC50 = 0.869 μM) against human pancreatic ductal adenocarcinoma cell MIA PaCa-2 compared to the reference chloroquine with (EC50 = 14 μM). Thus, the model showed good correlative and predictive ability. Docking studies was performed for designed compounds, docking analysis showed the best compound 1 with high docking affinity of -24.8616 kcal/mol.

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.

In-silico quantitative structure-activity relationship (QSAR) study was performed to develop a model on a series of novel pyrazole derivatives containing acetamide moiety which exhibited considerable antiproliferative activity against human colorectal adenocarcinoma cell line HT-29. The model obtained has a correlation coefficient (r) of 0.9693, squared correlation coefficient (r2) of 0.9395 and a leave-one-out (LOO) cross-validation coefficient (Q2) value of 0.8744. The predictive power of the developed model was confirmed by the external validation which has an r2 value of 0.9488. 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 (22-36), results indicated that the compounds 26, 31, 35, and 36 showed the strongest antiproliferative activity with (IC50 = 0.182, 0.172, 0.166 and 0.024 μM, respectively) against human colorectal adenocarcinoma cell line HT-29 compared to the reference vemurafenib with (IC50 = 1.52 μM). Molecular docking was performed on the new designed compounds with the human colorectal adenocarcinoma cell line 5JRQ protein. The docking results showed that compounds 26, 31, 35, and 36 have docking affinity of -8.528, -5.932, 23.017 and 18.432 kcal/mol, respectively.