New Thiosemicarbazide Analogs as Antagonist of Nicotinic Muscarinic Receptors: Synthesis, In silico, and In vivo Screening

Some new thiosemicarbazide derivatives (5*a-5*b and 6a-6f) were synthesized by multiple steps approaches starting from substituted anilines. The synthesized compounds were evaluated for their muscle relaxant activity by an in silico docking study against nicotinic muscarinic receptor (protein database [PDB] ID: 2XNU) using AutoDock Vina and Biovia discovery studio tools. The rotarod test was also used to evaluate the muscle-relaxing activity of the compounds. The results were compared with generic diazepam to corroborate both research findings. In the in silico test, all the compounds showed 2–4 interactions with the target nicotinic muscarinic receptor (PDB ID- 2XNU) having binding affinities in the range of −5.8–−7.8 Kcal/mol. Among them, the 6a compound demonstrated the most remarkable relaxant activity with four hydrogen bond interactions with amino acids TYRC: 52, ILE C: 88, ALA C:90, and GLN C:119 of the target molecule. In addition, the rotarod test showed that compounds 5*a and 6d also had more muscle-relaxing effects than diazepam.