Theoretical and experimental investigation of thiourea derivatives: synthesis, crystal structure, in-silico and in-vitro biological evaluation

Aisha, Muhammad Asam Raza, Umme Farwa, Umer Rashid, Jan K.Maurin, Armand Budzianowski


  • Thiourea,
  • 2,2-Diphenyl-1-picrylhydrazyl,
  • Enzyme inhibition,
  • Density functional theory,
  • Docking studies


In this study, five different thiourea derivatives were synthesized from aryl amines according to the reported method. 1-Benzoyl-3-(4-methoxyphenyl)thiourea (2) was confirmed with single crystal XRD analysis while 1-benzoyl-3-phenylthiourea (1), 1-benzoyl-3-(4 hydroxyphenyl)thiourea (3), 1-benzoyl-3-(2-nitrophenyl) thiourea (4) and 1-benzoyl-3-p tolylthiourea (5) were elucidated with FTIR and NMR techniques. The geometry optimization of the targeted molecules was accomplished with density functional theory applying B3LYP function. The experimental (XRD) and calculated (DFT) bond angles and bond lengths were 31compared. The frontier molecular orbitals and molecular electrostatic potential were computed to determine the charge density distribution and possible sites for electrophilic and nucleophilic reactions of the crystalline compound. The synthesized compounds were evaluated as an anti-radical scavenger and enzyme (esterases and protease) inhibitor using in-vitro models. The results confirmed that the synthesized molecules have good anti-oxidant property while a moderate enzyme inhibiting activity. Docking study was conducted with acetylcholine and butyrylcholine esterase which suggested that molecules under study have a potential to inhibit these esterases and protease enzymes. On the basis of in-vitro studies, it is concluded that compound 2 is most active against all tested assays.