Development of novel indole‐linked pyrazoles as anticonvulsant agents: A molecular hybridization approach

Abstract A series of 3‐{2‐[1‐acetyl‐5‐(substitutedphenyl)‐4,5‐dihydropyrazol‐3‐yl]hydrazinylidene}‐1,3‐dihydro‐2 H ‐indol‐2‐ones 24–43 was synthesized using an appropriate synthetic route and evaluated experimentally by the maximal electroshock test. These compounds were evaluated for antidepressant and antianxiety activities. The most active compound, 3‐{2‐[1‐acetyl‐5‐(4‐chlorophenyl)‐4,5‐dihydropyrazol‐3‐yl]hydrazinylidene}‐1,3‐dihydro‐2 H ‐indol‐2‐one 25 , exhibited an ED 50 of 13.19 mmol/kg, a TD 50 of 43.49 mmol/kg, and a high protective index of 3.29, compared with the standard drug diazepam. To get insights into the intermolecular interactions, molecular docking studies were performed at the active site of the GABA A receptor and the MAO‐A enzyme. Molecular docking studies are also in agreement with the pharmacological evaluation with potent compounds, exhibiting docking scores of −1.5180 and 0.7458 for the GABA A receptor and MAO‐A, respectively. The 3D‐QSAR analysis was carried out by Vlife MDS engine 4.3.1, and a statistically reliable model with good predictive power ( r 2 = 0.7523, q 2 = 0.3773) was achieved. The 3D‐QSAR plots gave insights into the structure–activity relationship of these compounds, which may aid in the design of potent benzopyrrole derivatives as anticonvulsant agents. So, our research can make a great impact on those medicinal chemists who work on the development of anticonvulsant agents.