Epilepsy is a severe neurological illness that affects millions of people the globally and is characterized by unpredicted and intermittent seizures.This research aimed to investigate the antiepileptic and antioxidant properties of papaverine derivatives using in-silico, in-vitro, and in-vivo methods.Epileptic seizure was induced in Swiss albino mice of either gender by administering PTZ (pentylenetetrazol). The antioxidant potential of test compounds was computed using previously published DPPH assay methods with minor modifications, while In-silico experiments were conducted using Auto-dock Vina (1.5.6) software and post dock analysis was completed using Discovery Studio Visualizer. The results showed that both compounds have strong antioxidant potential, with a noticeable change in color when compared to ascorbic acid as a control, and very low mortality when anti-epileptic potential was observed. The development of seizures was greatly delayed at first, but after 30 minutes of PTZ, they were completely gone. Both synthesized derivatives also comply the "Lipinski's rule of 5", which states that after structural alterations, extensive investigations, and trials, the chemical products would be evaluated for epilepsy management in the future In-silico investigations demonstrated that ligands with sufficient hydrogen bonds, pi-pi bonds, and Vander-Waals forces have a suitable propensity to engage with the binding pocket of selected protein targets. The current investigation of papaverine derivatives and their binding affinities against gamma aminobutyric acid (GABA) protein may have a vital function in epilepsy aetiology, according to the results of the studies. H1 and H2 were further verified in vivo for their anticonvulsant and antioxidant therapeutic potential. This could lead to more research into neurological problems.
G.A. Miana, M. Kanwal, S. Maqsood, Z. Tariq, F. Ali Shah, H. Saddam, M. Umar Farooq and Arif U. Khan
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