含硫肽结构的噻肟酰胺衍生物的设计、合成与抗菌活性  

Design,Synthesis and Antibacterial Activities of Thioxime Amide Derivatives Containing Thiopeptide

作　　者：佘慧娴 陈阳密 杨家强 SHE Huixian;CHEN Yangmi;YANG Jiaqiang(School of Pharmacy,Zunyi Medical University,Zunyi 563000,China)

机构地区：[1]遵义医科大学药学院,遵义563000

出　　处：《高等学校化学学报》2025年第5期54-62,共9页Chemical Journal of Chinese Universities

基　　金：贵州省科技计划项目(批准号:黔科合基础-ZK[2024]一般265);国家级大学生创新创业训练计划项目(批准号:202310661006)资助.

摘　　要：为了获取新型抗菌活性化合物,运用药效团拼合原理,将氨基噻唑、肟和硫肽结构通过酰胺键组合,设计合成了24个含硫肽结构的噻肟酰胺衍生物;经核磁共振波谱(^(1)H NMR,^(13)C NMR)和元素分析确证了其结构.活性测试结果表明,该类衍生物对革兰氏阳性菌有较显著活性,目标化合物5u对金黄色葡萄球菌(S.aureus)和耐甲氧西林金黄色葡萄球菌(MRSA)的最小抑菌浓度(MIC)分别为0.25和2μg/mL,化合物5v对S.aureus和MRSA的MIC值分别为0.5和2μg/mL,其抗S.aureus活性优于对照药苯唑西林(MIC=0.5μg/mL)或与之相当,抗MRSA活性显著,远优于对照药苯唑西林(MIC>128μg/mL),可作为抗菌候选化合物进行深入研究.In order to obtain novel antibacterial compounds,using the principle of pharmacophore assembly,twentyfour novel thioxime amide derivatives containing thiopeptide were designed and synthesized by combining active fragments of amino thiazole,oxime and thiopeptides,and confirmed by means of nuclear magnetic resonance hydrogen spectroscopy(^(1)H NMR),nuclear magnetic resonance carbon spectroscopy(^(13)C NMR)and elemental analysis.The antibacterial activities test results showed that these derivatives have significant activity against Gram positive bacteria.the minimum inhibitory concentration(MIC)values of compound 5u against S.aureus and methicillin-resistant S.aureus(MRSA)were 0.25μg/mL and 2μg/mL respectively,the MIC values of 5v against S.aureus and MRSA were 0.5μg/mL and 2μg/mL,respectively.Its anti-S.aureus activity was superior to that of the control drug oxacillin(MIC=0.5μg/mL)or relatively,and its anti-MRSA activity was significantly better than that of the control drug(MIC>128μg/mL),which will be further developed as novel candidates for antibacterial drugs.

关 键 词：硫肽 噻肟酰胺衍生物 药物设计 合成 抗菌活性 

分 类 号：O626[理学—有机化学]