新型化合物舒达吡啶(WX-081)对脓肿分枝杆菌的抗菌活性  

Antibacterial activity of a new compound, Shudapyridine (WX-081), against Mycobacterium abscesses

作　　者：苏雷 刘丽娜 王庆枫[3] 初乃惠[3] 聂文娟[3] Su Lei;Liu Lina;Wang Qingfeng;Chu Naihui;Nie Wenjuan(Inpatient WardⅠ,Tuberculosis Prevention and Control Institute of Anyang City,Henan Province,Anyang 455000,China;Inpatient WardⅢ,Respiratory and Critical Care Medicine Department,Third People’s Hospital of Hengshui City,Hebei Province,Hengshui 053000,China;Tuberculosis DepartmentⅠ,Beijing Chest Hospital,Capital Medical University,Beijing 101149,China)

机构地区：[1]河南省安阳市结核病防治所住院一病区,安阳455000 [2]河北省衡水市第三人民医院呼吸与危重症医学科三病区,衡水053000 [3]首都医科大学附属北京胸科医院结核一科,北京101149

出　　处：《中国防痨杂志》2023年第12期1147-1151,共5页Chinese Journal of Antituberculosis

基　　金：国家自然科学基金(82100002);北京市卫生健康委员会卫生健康科技成果和适宜技术课题(BHTPP2022083)。

摘　　要：目的:分析舒达吡啶(WX-081)抗脓肿分枝杆菌的体外及体内活性。方法:选取脓肿分枝杆菌标准株ATCC19977和7株脓肿分枝杆菌临床分离株,进行WX-081对脓肿分枝杆菌最低抑菌浓度(minimal inhibitory concentration,MIC)测定。为了进一步评价WX-081对脓肿分枝杆菌体内活性,选取AB型野生斑马鱼,构建脓肿分枝杆菌感染斑马鱼模型,对WX-081、贝达喹啉和阿奇霉素进行最大耐受浓度(maximum talerated concentration,MTC)检测,评估WX-081对脓肿分枝杆菌的抑菌效果。结果:WX-081对1株脓肿分枝杆菌标准株和7株临床分离株的体外MIC范围为0.7813~1.5625μg/ml。斑马鱼对阿奇霉素、贝达喹啉和WX-081的MTC分别为62.50μg/ml、15.60μg/ml和62.50μg/ml。WX-081浓度为11.95μg/ml、3.91μg/ml、7.81μg/ml、15.60μg/ml、31.20μg/ml、62.50μg/ml时斑马鱼全身荧光强度分别为535952±23902、520519±18208、492988±17182、462296±14360、419947±13302、375347±11359;斑马鱼头部荧光强度分别为101579±6065、101495±10160、93190±5468、89877±10333、76778±4906、70976±5726;随WX-081浓度升高逐渐下降,且均分别明显低于未用药的感染动物模型组(斑马鱼全身荧光强度为671089±22305;斑马鱼头部荧光强度为671089±22305),差异均有统计学意义(斑马鱼全身荧光强度比较:t值分别为4.134、5.229、6.326、7.871、9.670、11.815,P值均<0.001;斑马鱼头部荧光强度比较:t值分别为2.639、2.170、3.444、2.872、4.999、5.336,P值均<0.001)。斑马鱼受精后第4~9天,WX-081浓度为1.95μg/ml、3.91μg/ml和7.81μg/ml时,斑马鱼死亡率分别为90.0%(54/60)、85.0%(51/60)和81.7%(49/60),随着WX-081浓度逐渐升高死亡率逐渐下降(P<0.05)。结论:WX-081有效抑制了脓肿分枝杆菌在体外和体内的生长,延长了感染脓肿分枝杆菌斑马鱼的存活时间,显示出其对脓肿分枝杆菌较好的抗菌活性。Objective:To analyze the in vitro and in vivo activity of Sudapyridine(WX-081)against Mycobacterium abscess.Methods:The standard strain ATCC19977 and 7 clinical isolates of Mycobacterium abscess were selected,and the minimum inhibitory concentration(MIC)of WX-081 against Mycobacterium abscess were measured.In order to further evaluate the in vivo activity of WX-081 against Mycobacterium abscesses,AB type wild zebrafish was selected to construct an infection model of Mycobacterium abscesses.The maximum tolerated concentration(MTC)of WX-081,betaquiline,and azithromycin were tested to evaluate the antibacterial effect of WX-081 against Mycobacterium abscesses.Results:The in vitro MIC range of WX-081 for 1 standard strain of Mycobacterium abscess and 7 clinical isolates was 0.7813-1.5625μg/ml.The MTCs of zebrafish against azithromycin,betaquiline,and WX-081 were 62.50μg/ml,15.60μg/ml,and 62.50μg/ml,respectively.When the concentrations of WX-081 were 11.95μg/ml,3.91μg/ml,7.81μg/ml,15.60μg/ml,31.20μg/ml,and 62.50μg/ml,the whole body fluorescence intensities of zebrafish were 535952±23902,520519±18208,492988±17182,462296±14360,419947±13302,and 375347±11359,respectively;the fluorescence intensities of zebrafish head were 101579±6065,101495±10160,93190±5468,89877±10333,76778±4906,and 70976±5726,respectively;with the increase of WX-081 concentration,the values gradually decreased and were lower than those of the untreated infected animal model group(zebrafish whole body fluorescence intensity was 671089±22305;zebrafish head fluorescence intensity was 671089±22305,the differences were statistically significant(comparison of whole body fluorescence intensity of zebrafish:t values were 4.134,5.229,6.326,7.871,9.670,and 11.815,respectively,all P<0.001;comparison of head fluorescence intensity of zebrafish:t values were 2.639,2.170,3.444,2.872,4.999,and 5.336,respectively,all P<0.001).On the 4th to 9th day after fertilization,when the WX-081 concentrations of 1.95μg/ml,3.91μg/ml and 7.81μg/ml,the mort

关 键 词：非典型性细菌 分枝杆菌感染 抗菌药 舒达吡啶(WX-081) 

分 类 号：R978[医药卫生—药品] R37[医药卫生—药学]