Synthesis characterization and pharmacological screening of some newer 1 5 benzothiazepine derivatives

Abstract

Aims: Designing of a new series of 1,5-Benzothiazepines and evaluate their in-vivo anticonvulsant activity furthermore safety profile studies by acute oral toxicity. newlineBackground: Epilepsy is a dangerous neurological disease affects over 50 million people globally. The issue with the current situation is that there are many antiepileptic drugs present in the market, but they are ineffective, have a variety of adverse effects. Therefore, it is vital to develop new antiepileptic drugs or modify existing ones. newlineMethods: All computational studies were performed using SwissDock software. The purity of compounds checked by TLC, m.p, and elemental analysis. The chemical structures confirmed by FTIR, 1H-NMR and mass spectroscopy. Evaluation of pharmacological activity in phase I anticonvulsant activity. In phase II, the most active compounds were evaluated quantitatively. Acute oral toxicity evaluation was carried out under the OECD guiding for most potent compounds. newlineResults: Phase I anticonvulsant screenining most of the derivatives, with the exception of compounds A5, A6, A7, B9, B10, B11, Bl2, B13, B14, C2, C4, C6, C8, C9, C10, C11, C12, C13, C14, C16, C18, and C20, significant efficacy at 30 and 100 mg/kg without neurotoxin. After 0.5 hours, the compounds A3, B5, and C5 showed protection against MES-induced seizures at dose of 30 mg/kg, and this protection persisted at the same level after 4 hours. In phase II anticonvulsant screening, the most active compounds A3, B5, and C5 showed, ED50 of 16.8, 25.6, and 28.4, TD50 of 368.5, 324.3, and 295.6, and PI of 21.93, 12.66, and 10.5 respectively, which is higher than Phenytoin as standard drug. Acute oral toxicity studies, the compounds A3, B5, and C5 are safe and non-toxic up to doses of 2000 mg/kg. newlineConclusion: The most notable synthetic compounds A3, B5, and C5 were discovered as a major class of anticonvulsants, and they demonstrated virtually comparable anticonvulsant efficacy with remarkably reduced neurotoxicity. newline newline