Design, Synthesis, and Anti-tuberculosis Activity of Streptomycin Derivatives
文献类型:期刊论文
作者 | Zhang, Yinyong1,2,4; Zhao, Wenhao3; Yang, Yushe1,4; Zhou, Xianli2,5; Guo, Bin1,4 |
刊名 | LETTERS IN DRUG DESIGN & DISCOVERY |
出版日期 | 2024 |
卷号 | 21期号:4页码:738-748 |
ISSN号 | 1570-1808 |
关键词 | Multidrug-resistant hydrazine hydrazide sulfonyl hydrazide siderophore synthesis anti-tuberculosis activity |
DOI | 10.2174/1570180820666230116144553 |
通讯作者 | Zhou, Xianli(zhouxl@swjtu.edu.cn) ; Guo, Bin(guobin@simm.ac.cn) |
英文摘要 | Background: The treatment of tuberculosis has been a serious medical and health problem that needs to be solved urgently. Streptomycin has been one of the important anti-tuberculosis drugs for decades; however, no systematic structural modification of streptomycin has been done, which means that the anti-tuberculosis ability of streptomycin derivatives deserves further exploration.Objective: In this study, we investigated the effect of systematic structural modification of the aldehyde groups in streptomycin on its anti-tuberculosis activity.Methods: Streptomycin was selected as the lead compound, and its aldehyde group was modified to obtain hydrazone, amino hydrazide, and sulfonyl hydrazide derivatives, respectively. In addition, siderophore fragments were introduced into streptomycin. The anti-tuberculosis activities of the new compounds against H37Rv were evaluated.Results: A total of 21 novel streptomycin derivatives have been designed and synthesized. All compounds were characterized with 1H NMR, 13C NMR, and HRMS. The preliminary bioactivity test showed that most analogues bearing hydrazine, acylhydrazine, or sulfonyl hydrazine, such as 12a, 13a-d and 15a-f, possessed potent anti-tuberculosis activity with MIC value of 2 mu g/mL, which was comparable to streptomycin, while secondary amine or siderophore derivatives caused a dramatic reduction in activity.Conclusion: The structural modification and structure-activity relationship of the aldehyde group of streptomycin were systematically studied for the first time. The results showed that the aldehyde group was not necessary for exhibiting its activity. It was well tolerated when the aldehyde group was converted into hydrazine, acylhydrazine, or sulfonyl hydrazine. These novel analogues provide potential lead structures for further modification in the future. |
WOS关键词 | EXTENSIVELY DRUG-RESISTANT ; TUBERCULOSIS ; BEDAQUILINE ; BINDING ; POTENT |
WOS研究方向 | Pharmacology & Pharmacy |
语种 | 英语 |
出版者 | BENTHAM SCIENCE PUBL LTD |
WOS记录号 | WOS:001143518200001 |
源URL | [http://119.78.100.183/handle/2S10ELR8/309073] |
专题 | 中国科学院上海药物研究所 |
通讯作者 | Zhou, Xianli; Guo, Bin |
作者单位 | 1.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China 2.Southwest Jiaotong Univ, Sichuan Engn Res Ctr Biomimet Synth Nat Drugs, Sch Life Sci & Engn, Chengdu 610031, Peoples R China 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.Southwest Jiaotong Univ, Affiliated Hosp, Peoples Hosp Chengdu 3, Chengdu 610000, Peoples R China |
推荐引用方式 GB/T 7714 | Zhang, Yinyong,Zhao, Wenhao,Yang, Yushe,et al. Design, Synthesis, and Anti-tuberculosis Activity of Streptomycin Derivatives[J]. LETTERS IN DRUG DESIGN & DISCOVERY,2024,21(4):738-748. |
APA | Zhang, Yinyong,Zhao, Wenhao,Yang, Yushe,Zhou, Xianli,&Guo, Bin.(2024).Design, Synthesis, and Anti-tuberculosis Activity of Streptomycin Derivatives.LETTERS IN DRUG DESIGN & DISCOVERY,21(4),738-748. |
MLA | Zhang, Yinyong,et al."Design, Synthesis, and Anti-tuberculosis Activity of Streptomycin Derivatives".LETTERS IN DRUG DESIGN & DISCOVERY 21.4(2024):738-748. |
入库方式: OAI收割
来源:上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。