Study, Docking, In Silico ADME and Bio-Evaluation of Novel Hetero-Aromatic Amino Acid Derivatives as Potential Anti-Epileptic Agents

Alshehri, Faez F; Alshehri, Zafer S; Alhjlah, Sharif; Salama, Nagwan M; Alamshany, Zahra M; Arshad, Mohammed F; Elkirdasye, Ahmed F; Hassan, Allam A.

doi:10.21608/ejchem.2023.232868.8534

Study, Docking, In Silico ADME and Bio-Evaluation of Novel Hetero-Aromatic Amino Acid Derivatives as Potential Anti-Epileptic Agents

Document Type : Original Article

Authors

¹ Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Shaqra 11961, Saudi Arabia

² Department of Medical Pharmacology, Faculty of Medicine, Cairo University, Egypt.

³ Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21551, Saudi Arabia

⁴ Department of Research and Scientific Communications, Isthmus Research and Publishing House, U-13, Near Badi Masjid, Pulpehlad Pur, New Delhi 110044, India

⁵ Departmentof Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, 32897, Egypt.

⁶ Department of Chemistry, Faculty of Science, Suez University, Suez 43221, Egypt

10.21608/ejchem.2023.232868.8534

Abstract

A series of 1-(3-(1H-indol-3-yl)-1-(naphthalen-2-yl)allyl)-1,4-dihydroquinoline-4-carboxylic acid analogues (Va-j) were prepared, then tested for anticonvulsant efficacy. The analogues were tested using "gold standard procedures," which showed notable activity, particularly in chemically induced seizures. In the MES model and the scPTZ model, compounds Vf, Ve, Vg, and Vc were identified to be the most potent of the series. In order to assess motor damage, all synthetic analogues were also tested for acute neurotoxicity using the rotarod method. For the most part, all synthetic counterparts passed the test. The research also offers ADME predictions for all 10 congeners produced and carefully analysed each parameter. Additionally, the GABA-A target protein was used in research on molecular docking. The results of molecular docking revealed significant interactions at the active site of GABA-A with Val B:199, Arg A:180, Phen B:200, Ala B:201 and Lys A:173, and the outcomes were good and in agreement with in vivo findings. The compounds with EDG at position 6 or unsubstituted analogues were found to be most active where as those with electron donating group have less activity. New anticonvulsant medications may be created as a result of more research on these substances.

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