Molecular docking study and anticonvulsant activity of synthesized 4-((4,6-dimethyl-6H-1,3-thiazin-2-yl)phenylsulfonyl)urea/thiourea derivatives

Abstract

A new series of 1-(4-substitutedphenyl)-3-(4-(4,6-dimethyl-6H-1,3-thiazin-2-yl)phenylsulfon-yl)urea/thiourea (3a–l) derivatives were synthesized and screened for anticonvulsant activity by maximal electro shock (MES) and pentylenetetrazole (PTZ) induced convulsant model. All the derivatives were evaluated for neurotoxicity measures by rotarod method. Structures of synthesized compounds were established by spectroscopic techniques and elemental analysis. Pharmacological results were justified by the data obtained from the molecular docking studies along with the drug likeness and drug scores. From the experimental results, compounds 3a, 3b and 3c were found to be significantly effective. Out of these the chloro substituted derivative 1-(4-(4,6-dimethyl-6H-1,3-thiazin-2-yl)phenylsulfonyl)-3-(4-hydroxyphen-yl)urea (3c) was the most active convulsion protective compound. From the evaluation results it was concluded that the sulfonylurea series is better and safer than the sulfonylthiourea for anticonvulsant activity. Keywords: Anticonvulsant, Sulfonylurea, Molecular docking, Neurotoxicity, Rotarod, Drug likeness