Methicillin-resistant Staphylococcus aureus (MRSA) is one of causative bacteria for hospital- and community-acquired infections. In order to overcome MRSA infection, we synthesized compound A, a lincomycin derivative, and evaluated the biological properties. The MIC₅₀ and MIC₉₀ values of compound A against MRSA clinical isolates, which were susceptible to clindamycin, from infected skin in Japan were 0.12 and 0.25 μg ml⁻¹, respectively, and those against hospital-acquired MRSA with clindamycin resistance were 1.0 and 2.0 μg ml⁻¹, respectively. Linezolid non-susceptible MRSA selected in the laboratory had mutations in the 23S rRNA gene and exhibited cross-resistance to compound A. MRSA non-susceptible to compound A selected in laboratory was not cross-resistant to linezolid, implying that the binding site to 23S rRNA partly overlaps with clindamycin and linezolid. The in vivo efficacies of compound A against mouse skin abscess model infected with clindamycin-susceptible and -resistant MRSA were superior to those of clindamycin and linezolid, respectively. The well-known linezolid-induced myelosuppression is caused by its inhibitory effect on mitochondrial function, but inhibition was weaker for compound A than that of linezolid. In short, compound A has broader anti-MRSA activities than clindamycin and linezolid due to additional binding site, and demonstrated preferable safety profile as a potential anti-MRSA drug.

耐甲氧西林金黄色葡萄球菌(MRSA) 是医院和社区获得性感染的致病菌之一。为了克服MRSA感染，我们合成了化合物A，一种林可霉素衍生物，并评估了其生物学特性。化合物A对来自日本感染皮肤的对克林霉素敏感的MRSA临床分离株的MIC ₅₀和MIC ₉₀值分别为0.12和0.25 μg ml ^-1，而对具有克林霉素耐药性的医院获得性MRSA的MIC ₅₀和MIC ₉₀值分别为1.0和0.25 μg ml ^-1。 2.0 微克毫升^-1， 分别。实验室选择的利奈唑胺非敏感 MRSA 23S rRNA 基因发生突变，对化合物 A 表现出交叉耐药性。 rRNA 与克林霉素和利奈唑胺部分重叠。化合物A对克林霉素敏感和耐药MRSA感染的小鼠皮肤脓肿模型的体内疗效分别优于克林霉素和利奈唑胺。众所周知的利奈唑胺诱导的骨髓抑制是由其对线粒体功能的抑制作用引起的，但化合物 A 的抑制作用比利奈唑胺弱。简而言之，由于额外的结合位点，化合物 A 比克林霉素和利奈唑胺具有更广泛的抗 MRSA 活性，