Synthesis, Characterization, In Silico and In Vivo Evaluation of Benzimidazole‐Bearing Quinoline Schiff Bases as New Anticonvulsant Agents

• Published in: ChemistrySelect (Weinheim) 2023-06, Vol.8 (21), p.n/a
• Main Authors: Shabana, Km, Salahuddin, Mazumder, Avijit, Singh, Himanshu, Kumar, Rajnish, Tyagi, Sonakshi, Datt, Vimal, Shankar Sharma, Abhishek, Shahar Yar, Mohammad, Jawed Ahsan, Mohamed, Kumar Yadav, Ranjeet
• Format: Article
• Language: English
• Subjects: Anticonvulsant Activity; Benzimidazole; Benzimidazole bearing Quinoline; In silico and In vivo evaluation; Quinoline
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202300209

Nitrogen‐containing hybrid heterocyclic compounds have been gaining attention in the field of drug discovery and development due to their diverse pharmacological activities and relatively low toxicity. This study aimed to synthesize a series of new quinoline‐bearing amino acid‐derived benzimidazole derivatives i. e. 3‐{[1‐(1H‐Benzoimidazol‐2‐yl)‐subsituted‐methyl}‐4a,8a‐ dihydro‐1H‐quinoline‐2‐one, and 3‐{[1‐(1H‐Benzoimidazol‐2‐yl)‐substituted‐methyl}‐3H‐ quinoline‐2‐thione. These compounds were synthesized by the condensation of 2‐oxo‐1,2‐dihydro‐quinoline‐3‐ carbaldehyde and 2‐the oxo‐1,2‐dihydro‐quinoline‐3‐carbaldehyde with various substituted 1‐(1H‐benzimidazole‐2‐yl)‐methylamine. After synthesizing the compound, it was subjected to various characterization techniques such as IR, 1HNMR, 13CNMR, and Mass spectroscopy. The synthesized compounds were evaluated for their potential as an anticonvulsant using the subcutaneous Pentylenetetrazol (scPTZ) method, and the results were compared with those obtained for phenytoin and carbamazepine, which were used as standard drugs. Among all the screened derivatives 4 d, 4 e, 5 a, and 5 b were found to be the most potent as compared to conventional drugs (phenytoin and carbamazepine). Also, the molecular docking analysis of the synthesized compounds showed that they share the same mechanism of action as phenytoin and carbamazepine, which involves the inhibition of voltage‐gated sodium channels. Additionally, the analysis revealed that these compounds also inhibit the NMDA receptor. Overall, the development of nitrogen‐containing hybrid heterocyclic compounds has the potential to significantly contribute to the discovery and development of new drugs with improved efficacy, selectivity, and safety profiles. Two new series of oxadiazoles (4 a–f and 5 a–f) were designed and synthesized. All compounds were evaluated In silico and In vivo for their docking and anticovulsant activity respectively. Among all the screened derivatives 4 d, 4 e, 5 a, and 5 b were found to be the most potent as compared to conventional drugs (phenytoin and carbamazepine). The docking score of the synthesized compouns ranges from −9.61 to −6.46.