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 antiseizure 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.

Novel N‐propylphthalimide‐ and 4‐vinylbenzyl‐substituted benzimidazole salts: Synthesis, characterization, and determination of their metal chelating effects and inhibition profiles against acetylcholinesterase and carbonic anhydrase enzymes

“…In addition, recently enzyme inhibition studies of NHC ligands such as imidazole, benzimidazole, and imidazolidine have been conducted. NHC ligands have been demonstrated to be highly active in enzyme inhibition studies …”

Some coumarins and benzoxazinones as potent paraoxonase 1 inhibitors

“…The synthesized compounds had been obtained in good yields between 43-92%. Characterization of the compounds had been elucidated by nuclear magnetic resonance (NMR), infrared (IR) and elemental analyses in satisfactory manner 40 . For evaluating the PON1 activity, all compounds were subjected to PON1 inhibition assay with paraoxon as substrate.…”

“…Co (Istanbul, Turkey). Thirteen coumarin and eight benzoxazinone derivatives were ready from our previous study and detailed 40 .…”

“…The compounds that were used in this study had remained from our previous study 40 . For one of the strongest inhibitors, we performed kinetic and molecular docking studies to obtain insights into binding mode of these compounds with key residues of the active site of PON1.…”

Novel NHC Precursors: Synthesis, Characterization, and Carbonic Anhydrase and Acetylcholinesterase Inhibitory Properties

“…Also, it has been known that there are a lot of studies about biological activities including antimicrobial and anticancer activities of metal complexes of NHC precursors. In recent years, it was reported a growing enzyme inhibition studies of NHC precursors .…”