Synthesis and Structure-Activity Relationships of Ring-Opened Bengamide Analogues against Methicillin-Resistant Staphylococcus aureus

摘要

Methicillin-resistant Staphylococcus aureus (MRSA) has become a major threat on public health because of the increase of clinically isolated strains that exhibit resistance to many antibiotics.Therefore,development of new antibiotics for the treatment of MRSA infection is a sustained challenge.We have previously identified a ring-opened bengamide analogue L472-2 that displays moderate activity against the growth of S.aureus.In our previous work,we started from L472-2 and identified a class of analogues containing alkynyl groups which have the potential to activate SaClpP activity but moderate antibacterial activity.Herein,we focused on the antibacterial activity of L472-2,and a novel series of ring-opened bengamide analogues were synthesized and their activities were evaluated against MRSA.By conducting a compact analysis of the structure-activity relationships (SAR) of these analogues,we found that an adamantane ethanol ester bengamide 2j showed excellent antibacterial activity towards six S.aureus strains,including MRSA,while it does not activate ClpP.Therefore,these bengamide analogues represent a new class of candidates that suppress MRSA viability.