Synthesis and in vitro activity tests of N-benzoyl-N'-phenylthiourea derivatives as macrophage migration inhibitory factor

Context: The COVID-19 pandemic in 2020 resulted in widespread mortalities due to cytokine storms in the affected patients. Macrophage migration inhibitory factor (MIF) is one of the most interesting targets in developing anti-COVID-19 drugs. Some thiourea compounds have been identified as having potential as MIF inhibitors.Aims: To investigate MIF inhibitory activity of N-benzoyl-N'-phenylthiourea derivatives.Methods: The study consists of in-silico activity prediction of designed compounds using a molecular docking approach against MIF protein (PDB ID: 1LJT). Afterwards, the designed compounds were synthesized and tested in vitro using the tautomerase activity approach.Results: The molecular docking study showed that all designed compounds possess comparable docking scores to the native ligand of the protein. MIF Assay performed on compounds (1) and (2) indicated a decrease in tautomerase activity of the MIF target protein of only 10.1 and 6.2%, respectively, compared to the positive control.Conclusions: In silico results predicted better bioactivity against MIF protein, but the result does not translate to the in vitro assay, where two of the designed compounds possess only low inhibitory activity.

Automated summary

This study aims to investigate the MIF inhibitory activity of N-benzoyl-N'-phenylthiourea derivatives. The molecular docking study predicted better bioactivity against MIF protein, but the in vitro assay showed only low inhibitory activity for two of the designed compounds.