Background- A series of aromatic sulfonamides incorporating coumarin as a lead were designed a for epilepsy target. Carbonic anhydrase is an influential target for the expansion of lead to treat epilepsy. Experimentally known carbonic anhydrase determents were identified to develop ligand based pharmacophore for anticonvulsant model. The X-ray crystallographic make-up of carbonic anhydrases with several inhibitors were utilized to develop ten energy optimized structure based (E- pharmacophore model). Pharmacophore matched candidates were utilized for docking to reclaim hits with scaffolds. The molecules having diverse structures, high docking score and low binding energy for various crystal structures of carbonic anhydrase were selected as final hits (leads). DFT is utilized to get electronic features of hits. The docking study of ligands by discovery studio had helped to establish binding interactions. The known carbonic anhydrase was reused for the development of pharmacophore hypothesis DHHRR. Based on Insilco process we came across structurally diverse hits as noncompetitive carbonic anhydrase inhibitors with better ADME. The best three hits 4, 6 and 17 were nontoxic and were selective carbonic anhydrase inhibitors with the IC50 values respectively (IC50 2.01, 2.59, 2.469). The study describes that the combined pharmacophore appeal to identify various hits which have good binding affinity for the active site of enzyme in all feasible bioactive conformations.
The combination of different heterocyclic rings to form a multifunctional compound is a new approach
to get the potent and selective compounds, which can act as antiepileptic drugs. In this study we
designed and synthesized the hybrid of the coumarin ring with sulfonamide moiety. Coumarin
sulfonamide hybrids (CS1-CS7) were synthesized by Knoevenagel condensation of methyl
anilinosulfonyl acetate with substituted salicyaldehyde in the presence of catalytic base. The synthesized
hybrid compounds were characterized by means of mass, 1H & 13C NMR and FTIR spectroscopy,
moreover antiepileptic activity was screened through seizure model of epilepsy using pentylenetetrazole
and maximal electroshock. According to results, compound CS-2 remained to be highest potent and
presented significant protection at 60 mg/kg in both the seizure models. Furthermore, compound
CS-2 was also evaluated for biochemical and a histopathological study in which no significant results
were obtained. In addition to former activities, compound CS-2 was also examined for liver toxicity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.