Design, synthesis, and molecular docking study of benzothiazolotriazine derivatives for anticonvulsant potential

A series of benzothiazolotriazine derivatives (4a –k) was designed, synthesized, and evaluated for their anticonvulsant activity by MES and scPTZ assays. 8 ‐Chloro‐4‐(2‐chlorocyclohexa‐1,5‐dien‐1‐yl)‐2‐((4‐methoxybenzyl)thio)‐10aH‐benzo[4,5]thiazolo[3,2a][1,3,5]triazine4e as the most promising agent in the series indicated that the presence of a methoxy group at the lipophilic aryl ring confers high anticonvulsant potency. AbstractA series of newer benzothiazolotriazine derivatives (4a –k) was designed, synthesized, and characterized as anticonvulsant agents against the two classically used MES and scPTZ animal models. The synthesized derivatives were testedin vivo in both the animal models, followed by a neurotoxicity study by the rotarod method. Compound4e, 8 ‐chloro‐4‐(2‐chlorocyclohexa‐1,5‐dien‐1‐yl)‐2‐((4‐methoxybenzyl)thio)‐10aH‐benzo[4,5]thiazolo[3,2a][1,3,5]triazine was found most promising among the series in both the animal models, with no neurotoxicity. From this it may be confirmed that the presence of a methoxy (OCH3) group at the lipophilic aryl ring was showing high anticonvulsant potency. In the molecular modeling study, compound4e (docking score  = −8.70) showed important hydrogen bond interaction with the amino acids LYS 329, SER 137, GLY 136 and π–π interactions with PHE 189 at the active site of GABA‐AT. These derivatives can be further explored for the development of newer/novel anticonvu...
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: FULL PAPER Source Type: research