Synthesis and Design of novel morpholinyl mannich bases for Potential Inhibitory Activity of SARS-CoV-2 Main Protease

Abstract

In this study, a new mannich base 1-(2H-1,3-benzodioxol-5-yl)-3-(morpholin-4-yl)propan-1-one (Mor) was successfully prepared in good yield. The structure of the title compound was elucidated by 1H-NMR, FT-IR, UV-Vis and electron-impact mass spectroscopy. The inhibitory activity of Mor against SARS-CoV-2 main protease (Mpro) was investigated by means of molecular docking approach. Mor showed excellent binding affinity to the active residues of Mpro with low binding score energy. Further improvements in the results were obtained by four designated analogues to Mor, characterized by the introduction of different methoxyl and hydroxyl substituents. The hydroxyl groups in Mor analogues significantly improve the binding affinity to the active site of Mpro to 56%, the binding energy to -6.3 kcal/mol, as well as the ability to form hydrogen bonds compared with nirmatrelvir as the reference Mpro inhibitor.