Synthesis, spectroscopic characterization of novel phthalimides derivatives bearing a 1,2,3-triazole unit and examination as potential SARS-CoV-2 inhibitors via studies.

In the present study, novel phthalimide derivatives (-) and () bearing a 1,2,3-triazole subunit were synthesized via CuAAC reactions and characterized by H, C NMR, HR-MS, and FT-IR analyses. To support the fight against SARS-CoV-2, molecular docking studies were carried out to examine their interactions with the proteins of SARS-CoV-2 (Mpro and PLpro) and the protein-protein interactions (PPI) between the ACE2-spike (S1) in comparison with various inhibitors reported to be active by experiments. The ligand-protein stabilities of compounds -Mpro, -PLpro, and -'ACE2-S1' showing the best binding energy and predicted inhibition constant values (Ki) were examined by molecular dynamics simulation studies. Finally, ADMET properties of the target compounds were investigated using the Swiss ADME and ProTox-II web tools. According to results, all phthalimide analogs may block the PPI between S1 and ACE2. The compounds may also inhibit the progression of the Mpro, and PLpro proteins of SARS-CoV-2. Additionally, it has been estimated that the compounds are suitable for oral administration and exhibit low levels of toxicity.