Synthesis and Structure‐Activity Relationships of Ring‐Opened Bengamide Analogues against Methicillin‐Resistant Staphylococcus aureus†,Chinese Journal of Chemistry

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Synthesis and Structure‐Activity Relationships of Ring‐Opened Bengamide Analogues against Methicillin‐Resistant Staphylococcus aureus†
Chinese Journal of Chemistry ( IF 5.5 ) Pub Date : 2020-10-30 , DOI: 10.1002/cjoc.202000502
Chen‐Xi Yu _{1,

2} , Bing‐Yan Wei _{1,

3} , Xue‐Qing Kong _{1,

2} , Cai‐Guang Yang _{1,

3} , Fa‐Jun Nan _{1,

4}

Affiliation

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.

中文翻译：

开环明酰胺类似物对耐甲氧西林金黄色葡萄球菌†的合成及其构效关系†

耐甲氧西林金黄色葡萄球菌（MRSA）已成为对公共卫生的主要威胁，因为临床分离出的菌株对多种抗生素具有耐药性。因此，开发用于治疗MRSA感染的新抗生素是持续的挑战。先前我们已经确定了开环的苯甲酰胺类似物L472-2，其对金黄色葡萄球菌的生长具有中等活性。在我们之前的工作中，我们从L472-2开始，鉴定出一类含有炔基的类似物，这些类似物具有激活SaClpP活性但具有中等抗菌活性的潜力。在这里，我们集中于L472-2的抗菌活性，合成了一系列新的开环的苯甲酰胺类似物，并评估了它们对MRSA的活性。通过对这些类似物的构效关系（SAR）进行紧凑分析，我们发现金刚烷乙醇酯苯甲酰胺2j对包括MRSA在内的6种金黄色葡萄球菌菌株均显示出优异的抗菌活性，但它并未激活ClpP。因此，这些苯甲酰胺类似物代表了抑制MRSA生存力的一类新候选人。

更新日期：2020-10-30

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