Design, Synthesis and Evaluation of Novel Pyrrolidinone-Based ACE2 Inhibitors: Preliminary Study

This study focuses on the rational design and synthesis of new pyrrolidinone derivatives aimed at inhibiting the ACE2 receptor, a key entry point for SARS-CoV-2. Building on structural insights from known inhibitors like MLN-4760, five compounds featuring a pyrrolidinone core, with some incorporating indole rings, were synthesized and characterized. Their inhibitory activity against ACE2 was evaluated in vitro, with compound 4 showing the most promising results, further confirmed through cytotoxicity assays and molecular docking studies. Docking analysis revealed favorable binding interactions within the ACE2 active site, supporting the potential of compound 4 as a therapeutic agent. These findings provide a foundation for future in vivo studies and highlight the potential development of novel therapeutics targeting ACE2-related diseases, including COVID-19.