一氧化碳的抗菌机制及其释放分子作为抗感染药物的可行性  

The bactericidal mechanisms of carbon monoxide and the feasibility of carbon monoxide-releasing molecules as anti-infective drugs

作　　者：吴根福[1] WU Gen-fu(College of Life Sciences,Zhejiang University,Hangzhou 310058,China)

机构地区：[1]浙江大学生命科学学院,浙江杭州310058

出　　处：《药学学报》2023年第4期891-898,共8页Acta Pharmaceutica Sinica

基　　金：浙江省自然科学基金资助项目(LY21C010003)。

摘　　要：介绍一氧化碳(CO)和CO释放分子的杀菌机制及其作为抗感染药物的可行性,为相关教学和研究工作提供参考。通过查阅文献,结合自身科研工作,对CO的杀菌机制及其作为抗感染药物的可行性进行综述。厌氧细菌通常能耐受高浓度CO,有些甚至能以CO为唯一的碳源或能源生长,但一些常见的致病菌对CO敏感。鉴于CO气体的剂量和施加部位不易控制,一批CO释放分子被合成出来。CO释放分子不但安全易控,杀菌效率比气态CO更高,对耐药菌株及其生物膜也具有很好的杀灭和抑制作用。CO主要与细胞内的血红素-Fe2+结合,阻断呼吸链电子传递,进而产生活性氧;CO还通过与金属元素的结合影响胞内离子平衡,进而触发自由基反应,破坏DNA等大分子。CO具有作用靶标多样,不易产生耐药性,与现有抗生素存在协同效应等优点,有望成为下一代抗感染药物。The bactericidal mechanism of carbon monoxide(CO)and the feasibility of CO-releasing molecules as anti-infective drugs were summarized by consulting scientific literature,combined with our own research work.Anaerobic bacteria are usually tolerant to high concentration of CO,and some can even grow with CO as sole carbon or energy source,but most pathogenic bacteria are sensitive to CO.In view of the difficulty of gaseous CO in controlling the applying dose and the action site,CO release molecules were synthesized.CO release molecules not only have higher bactericidal activities against common pathogenic bacteria than gaseous CO,but also have the ability to kill antibiotics-resistant bacteria and destroy their biofilms.CO mainly binds with heme-Fe2+in cells,interrupting the electron transfer of respiration chains,which would result in the generation of reactive oxygen species.CO can also disturb intracellular ion balance,which further triggers free radical reactions.Due to its diverse acting targets,uneasy to induce drug resistance,and synergistic effect with other antibiotics,CO is expected to be the next generation of anti-infection drugs.

关 键 词：一氧化碳 一氧化碳释放分子 血红素 活性氧 抗感染药 

分 类 号：R966[医药卫生—药理学]