Green by Design: Convergent Synthesis, Computational Analyses, and Activity Evaluation of New FXa Inhibitors Bearing Peptide Triazole Linking Units

Green chemistry implementation has led to promising results in waste reduction in the pharmaceutical industry. However, the early sustainable development of pharmaceutically active compounds and ingredients remains a considerable challenge. Herein, we wish to report a green synthesis of new pharmaceutically active peptide triazoles as potent factor Xa inhibitors, an important drug target associated with the treatment of diverse cardiovascular diseases. The new inhibitors were synthesized in three steps, featuring cycloaddition reactions (high atom economy), microwave-assisted organic synthesis (energy efficiency), and copper nanoparticle catalysis, thus featuring Earth-abundant metals. The molecules obtained showed FXa inhibition, with IC50-values as low as 17.2 mu M and no associated cytotoxicity in HEK293 and HeLa cells. These results showcase the environmental potential and chemical implications of the applied methodologies for the development of new molecules with pharmacological potential.

Automated summary

Implementation of green chemistry has shown promising results in waste reduction in the pharmaceutical industry. However, sustainable development of pharmaceutically active compounds and ingredients remains challenging. In this study, a green synthesis method was used to produce pharmaceutically active peptide triazoles as potent factor Xa inhibitors, important drug targets for cardiovascular diseases. The synthesis involved cycloaddition reactions with high atom economy, microwave-assisted organic synthesis for energy efficiency, and copper nanoparticle catalysis with Earth-abundant metals. The synthesized molecules demonstrated FXa inhibition with low IC50 values and no cytotoxicity in HEK293 and HeLa cells, highlighting the environmental potential and chemical implications of the applied methodologies for new molecule development.