Synthesis and In Silico Study of Some New <i>bis</i>-[1,3,4]thiadiazolimines and <i>bis</i>-Thiazolimines as Potential Inhibitors for SARS-CoV-2 Main Protease

Abstract

A novel series of bis-[1,3,4]thiadiazolimines, and bis-thiazolimines, with alkyl linker, were synthesized through general routes from cyclization of 1,1′-(hexane-1,6-diyl)bis(3-phenylthiourea) and hydrazonoyl halides or α-haloketones, respectively. Docking studies were applied to test the binding affinity of the synthesized products against the Mpro of SARS-CoV-2. The best compound, 5h, has average binding energy (−7.50 ± 0.58 kcal/mol) better than that of the positive controls O6K and N3 (−7.36 ± 0.34 and −6.36 ± 0.31 kcal/mol). Additionally, the docking poses (H-bonds and hydrophobic contacts) of the tested compounds against the Mpro using the PLIP web server were analyzed.

Keywords

• <i>bis</i>-(3-phenylthiourea)
• hydrazonoyl halides
• <i>α</i>-haloketones
• molecular docking
• SARS-CoV-2 M^pro