Antibiotic resistance evolves naturally through random mutation. Resistance to antimicrobials is an urgent public health crisis that requires coordinated global action. The ESKAPE bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are primarily responsible for the rise in resistant pathogens. There is an immediate requirement to identify a novel molecular scaffold with potent anti-microbial properties. We developed an efficient one-step synthesis of 2-benzylidene-3-oxobutanamide and its derivatives, which allowed the introduction of an α,β-unsaturated ketone moiety in the quest to identify a new molecular scaffold. Seven compounds exhibited very good antibacterial activity in vitro against WHO priority drug-resistant bacteria such as methicillin resistant Staphyloccus aureus (MRSA) and Acinetobacter baumannii-Multi drug resistant (MDR-AB). In cultured human embryonic kidney cells and hemolysis assays, the potent compounds displayed minimal toxicity. These findings suggest that these small molecules with excellent diversity have the potential to combat antibacterial resistance.

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2-亚苄基-3-氧代丁酰胺衍生物的合成及其对耐药病原体的抗菌活性

抗生素耐药性通过随机突变自然演变。抗菌药物耐药性是一场紧迫的公共卫生危机，需要全球采取协调一致的行动。ESKAPE 细菌（屎肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠杆菌属）是耐药病原体增加的主要原因。迫切需要确定一种具有有效抗微生物特性的新型分子支架。我们开发了一种有效的一步合成 2-亚苄基-3-氧代丁酰胺及其衍生物的方法，可以引入 α,β-不饱和酮部分，以寻求鉴定一种新的分子支架。七种化合物在体外对世界卫生组织重点耐药菌如耐甲氧西林金黄色葡萄球菌（MRSA）和多重耐药鲍曼不动杆菌（MDR-AB）表现出非常好的抗菌活性。在培养的人胚胎肾细胞和溶血试验中，这些有效的化合物显示出最小的毒性。这些发现表明，这些具有优异多样性的小分子具有对抗抗菌药物耐药性的潜力。