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‐2H‐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‐2H‐indol‐2‐one 25, exhibited an ED50 of 13.19 mmol/kg, a TD50 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 GABAA 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 GABAA 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 (r2 = 0.7523, q2 = 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.

Prediction of antiviral activity, cytotoxicity risks and molecular docking against HIV of constituents from marine algae

“…In addition, the toxicity of the metabolites of the selected molecules were analyzed. [14] For molecular docking, the best molecules and the control drugs were used: darunavir for protease and doravirine for reverse transcriptase. The crystal structures of HIV-1 reverse transcriptase with TNK-651 and of HIV protease with CKD ((S)-…”

Anticholinesterase and antioxidant activities of novel heterocyclic Schiff base derivatives containing an aryl sulfonate moiety

“…It is known that this class of compounds, which is one of the most active classes of heterocyclic compounds, indicates a broad spectrum of pharmacological activities. [36][37][38][39][40] Pyrazolones represent a very significant class of pyrazole family. [41,42] Pyrazolone nucleus has used in the production of a series of commercial medicaments so far is an important pharmacophore.…”

“…It is known that this class of compounds, which is one of the most active classes of heterocyclic compounds, indicates a broad spectrum of pharmacological activities. [ 36–40 ]…”

Synthesis and insecticidal activity of novel 1,2,4‐triazole containing amidine moiety

“…Molecular hybridization is a strategy that combines two or more bioactive substances or parts of them in a single molecule. It has been widely used in drug discovery [17][18][19][20]. Compared to the parent compounds, many hybrid derivatives possessed improved bioactivity and safety.…”