Coumarin or benzoxazinone based novel carbonic anhydrase inhibitors: synthesis,molecular docking and anticonvulsant studies |
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Authors: | Mert Olgun Karataş Harun Uslu Suat Sarı Mehmet Abdullah Alagöz Arzu Karakurt Bülent Alıcı |
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Affiliation: | 1. Department of Chemistry, Faculty of Arts and Science and;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Inonu University, Malatya, Turkey,;3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey, and |
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Abstract: | Among many others, coumarin derivatives are known to show human carbonic anhydrase (hCA) inhibitory activity. Since hCA inhibition is one of the underlying mechanisms that account for the activities of some antiepileptic drugs (AEDs), hCA inhibitors are expected to have anti-seizure properties. There are also several studies reporting compounds with an imidazole and/or benzimidazole moiety which exert these pharmacological properties. In this study, we prepared fifteen novel coumarin-bearing imidazolium and benzimidazolium chloride, nine novel benzoxazinone-bearing imidazolium and benzimidazolium chloride derivatives and evaluated their hCA inhibitory activities and along with fourteen previously synthesized derivatives we scanned their anticonvulsant effects. As all compounds inhibited purified hCA isoforms I and II, some of them also proved protective against Maximal electroshock seizure (MES) and ScMet induced seizures in mice. Molecular docking studies with selected coumarin derivatives have revealed that these compounds bind to the active pocket of the enzyme in a similar fashion to that previously described for coumarin derivatives. |
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Keywords: | Anticonvulsant benzoxazinone carbonic anhydrase coumarin epilepsy inhibition |
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