Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Design, synthesis and biological activities of 5H-dibenzo[b,f]azepine-5-carboxamide derivatives; Targeted hippocampal trypsin inhibition as a novel approach to treat epileptogenesis

Taha` Iqbal, Mohsin Abbas Khan, Irshad Ahmad , Fahad Mehmood Khan

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Pakistan;

For correspondence:- Irshad Ahmad Email: drirshad.iub@gmail.com Tel:+923006800703

Accepted: 5 February 2022 Published: 28 February 2021

Citation: Iqbal T, Khan MA, Ahmad I, Khan FM. Design, synthesis and biological activities of 5H-dibenzo[b,f]azepine-5-carboxamide derivatives; Targeted hippocampal trypsin inhibition as a novel approach to treat epileptogenesis. Trop J Pharm Res 2022; 21(2):303-312 doi: 10.4314/tjpr.v21i2.13

© 2022 The authors.
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Abstract

Purpose: To synthesize anticonvulsant drug derivatives that target protease-activated receptor generated epileptic seizures.

Method: Varieties of carbamazepine-based Schiff bases were designed with different aldehydes and ketones, and evaluated for in silico computer-aided drug design prediction of absorption, distribution, metabolism and excretion (ADME), and potential drug targets. The resultant compounds were synthesized and characterized by various spectroscopic techniques, including FTIR, ¹H-NMR and ¹³C-NMR, analysis. Thereafter, they were screened for antimicrobial, antioxidant and anticonvulsant potential.

Results: Prominent anti-protease potential was shown by C7 and C3 compounds and the order of activity was C7 > C3 > C5 > C2 > C6 > C4 > C2 > C1 (p < 0.05). The anticonvulsant activity of C7 and C5 was comparable with the standard drug; C3, C4, C6 and C8 had mild activity while C1 and C4 showed the least activity. The synthesized compounds exhibited significant (p < 0.05) antioxidant potential (rank order: C3 > C4 > C5 > C7 > C8 > C6 > C1 > C2) and antimicrobial activity against S. aureus and B. bronchiseptica (rank order: C5 > C2 > C8 > C1 > C4 > C3 > C7).

Conclusion: Synthesized derivatives retained their potential for anticonvulsant and antitrypsin activity, unlike their mother moiety, i.e., carbamazepine. The additional antibacterial activity effectively treats neurological disorders associated with bacterial infections.

Keywords: Carbamazepine, Epilepsy, Antibacterial, Proteases