Novel partially reversible NDM-1 inhibitors based on the naturally occurring houttuynin

In this study, we found that naturally occurring houttuynin and its sulfonate derivatives might be effective NDM-1 inhibitors with novel mechanism, i.e. the attribute of partially covalent inhibition of sulfonate derivatives of houttuynin against NDM-1. Primary structure-activity relationship study showed that both the long aliphatic side chain and the warhead of aldehyde group are vital for the efficiency against NDM-1. The homologs with longer chains (SNH-2 to SNH-5) displayed stronger inhibitory activities with IC50 range of 1.1-1.5 μM, while the shorter chain the weaker inhibition. Further synergistic experiments in cell level confirmed that all these 4 compounds (at 32 μg/mL) recovered the antibacterial activity of meropenem (MER) against E. coli BL21/pET15b-blaNDM-1.PMID:38583248 | DOI:10.1016/j.bioorg.2024.107328
Source: Bioorganic Chemistry - Category: Chemistry Authors: Source Type: research