Synthesis, anti-convulsant activity and molecular docking study of novel thiazole pyridazinone hybrid analogues

Bioorg Chem. 2020 Jun:99:103584. doi: 10.1016/j.bioorg.2020.103584. Epub 2020 Jan 27.

Abstract

Pyridazinone analogues have been known to be potential candidates for anticonvulsant agents. We have identified several pyridazinone-based anticonvulsant agents. As a continuation to our previous research, a series of hybrid pyridazinone-thiazole connected through amide linkage were designed and synthesized. Among these, compound SP-5F demonstrated significant anticonvulsant activity with median effective dose of 24.38 mg/kg (MES) and 88.23 mg/kg (scPTz). Results of GABA estimation showed a marked increase in the GABA level when compared with control. Molecular docking studies at the active site of GABA receptor, further confirmed the GABA modulatory effects of SP-5F.

Keywords: Anticonvulsant activity; GABA; Pharmacophore based drug design; Pyridazinone; Thiazole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / chemical synthesis
  • Anticonvulsants / chemistry
  • Anticonvulsants / therapeutic use*
  • Dose-Response Relationship, Drug
  • Electroshock
  • Female
  • Injections, Subcutaneous
  • Male
  • Mice
  • Molecular Docking Simulation*
  • Molecular Structure
  • Pentylenetetrazole / administration & dosage
  • Pyridazines / chemical synthesis
  • Pyridazines / chemistry
  • Pyridazines / therapeutic use*
  • Seizures / chemically induced
  • Seizures / drug therapy*
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry
  • Thiazoles / therapeutic use*

Substances

  • Anticonvulsants
  • Pyridazines
  • Thiazoles
  • Pentylenetetrazole