title: Coumarin or benzoxazinone based novel carbonic anhydrase inhibitors: synthesis, molecular docking and anticonvulsant studies.
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.
authors.affiliation: a Department of Chemistry, Faculty of Arts and Science and.
authors.forename: Mert Olgun
authors.initials: MO
authors.lastname: Karataş
authors.affiliation: b Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Inonu University , Malatya , Turkey .
authors.forename: Harun
authors.initials: H
authors.lastname: Uslu
authors.affiliation: c Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Hacettepe University , Ankara , Turkey , and.
authors.forename: Suat
authors.initials: S
authors.lastname: Sarı
authors.affiliation: b Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Inonu University , Malatya , Turkey .
authors.forename: Mehmet Abdullah
authors.initials: MA
authors.lastname: Alagöz
authors.affiliation: b Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Inonu University , Malatya , Turkey .
authors.forename: Arzu
authors.initials: A
authors.lastname: Karakurt
authors.affiliation: a Department of Chemistry, Faculty of Arts and Science and.
authors.forename: Bülent
authors.initials: B
authors.lastname: Alıcı
authors.affiliation: d Department of Chemistry, Faculty of Art and Sciences , Balikesir University , Balikesir , Turkey.
authors.forename: Cigdem
authors.initials: C
authors.lastname: Bilen
authors.affiliation: d Department of Chemistry, Faculty of Art and Sciences , Balikesir University , Balikesir , Turkey.
authors.forename: Emre
authors.initials: E
authors.lastname: Yavuz
authors.affiliation: d Department of Chemistry, Faculty of Art and Sciences , Balikesir University , Balikesir , Turkey.
authors.forename: Nahit
authors.initials: N
authors.lastname: Gencer
authors.affiliation: d Department of Chemistry, Faculty of Art and Sciences , Balikesir University , Balikesir , Turkey.
authors.forename: Oktay
authors.initials: O
authors.lastname: Arslan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D048588:Benzoxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002256:Carbonic Anhydrases / Q000378:metabolism; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004789:Enzyme Activation / Q000187:drug effects; D020128:Inhibitory Concentration 50; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D012640:Seizures / Q000188:drug therapy*; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D048588:Benzoxazines; D002257:Carbonic Anhydrase Inhibitors; D003374:Coumarins; D002256:Carbonic Anhydrases
keywords: Anticonvulsant; benzoxazinone; carbonic anhydrase; coumarin; epilepsy; inhibition