Design, Synthesis, and Biological Evaluation of Novel Arylomycins against Multidrug-Resistant Gram-Negative Bacteria
文献类型：期刊论文
| 作者 | Zhang, Yinyong2,3,4,5; Zhang, Dan2,3; Zhao, Wenhao2,3; Li, Hongyuan2,3; Lu, Zhengyu2,3; Guo, Bin2,3 ; Meng, Xin2,3; Zhou, Xianli1,4,5; Yang, Yushe2,3
|
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2024-04-10 |
| 页码 | 25 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.4c00018 |
| 通讯作者 | Zhou, Xianli(zhouxl@swjtu.edu.cn) ; Yang, Yushe(ysyang@simm.ac.cn) |
| 英文摘要 | G0775, an arylomycin-type SPase I inhibitor that is being evaluated in a preclinical study, exhibited potent antibacterial activities against some Gram-negative bacteria but meanwhile suffered defects such as a narrow antibacterial spectrum and poor pharmacokinetic properties. Herein, systematic structural modifications were carried out, including optimization of the macrocyclic skeleton, warheads, and lipophilic regions. The optimization culminated in the discovery of 138f, which showed more potent activity and a broader spectrum against clinically isolated carbapenem-resistant Gram-negative bacteria, especially against Acinetobacter baumannii and Pseudomonas aeruginosa. 162, the free amine of 138f, exhibited an excellent pharmacokinetic profile in rats. In a neutropenic mouse thigh model of infection with multidrug-resistant P. aeruginosa, the potent in vivo antibacterial efficacy of 162 was confirmed and superior to that of G0775 (3.5-log decrease vs 1.1-log decrease in colony-forming unit (CFU)). These results support 162 as a potential antimicrobial agent for further research. [GRAPHICS] . |
| WOS关键词 | I SIGNAL PEPTIDASE ; ANTIBIOTICS ; INHIBITORS ; MECHANISM ; SPECTRUM |
| 资助项目 | Youth Innovation Promotion Association of the Chinese Academy of Sciences[2021275] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001200254100001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/310786]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhou, Xianli; Yang, Yushe |
| 作者单位 | 1.Southwest Jiaotong Univ, Affiliated Hosp, Peoples Hosp Chengdu 3, Chengdu 610000, Sichuan, Peoples R China 2.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Southwest Jiaotong Univ, Sch Mat Sci & Engn, Key Lab Adv Technol Mat, Minister Educ, Chengdu 610031, Peoples R China 5.Southwest Jiaotong Univ, Sichuan Engn Res Ctr Biomimet Synth Nat Drugs, Sch Life Sci & Engn, Chengdu 610031, Sichuan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Yinyong,Zhang, Dan,Zhao, Wenhao,et al. Design, Synthesis, and Biological Evaluation of Novel Arylomycins against Multidrug-Resistant Gram-Negative Bacteria[J]. JOURNAL OF MEDICINAL CHEMISTRY,2024:25. |
| APA | Zhang, Yinyong.,Zhang, Dan.,Zhao, Wenhao.,Li, Hongyuan.,Lu, Zhengyu.,...&Yang, Yushe.(2024).Design, Synthesis, and Biological Evaluation of Novel Arylomycins against Multidrug-Resistant Gram-Negative Bacteria.JOURNAL OF MEDICINAL CHEMISTRY,25. |
| MLA | Zhang, Yinyong,et al."Design, Synthesis, and Biological Evaluation of Novel Arylomycins against Multidrug-Resistant Gram-Negative Bacteria".JOURNAL OF MEDICINAL CHEMISTRY (2024):25. |
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。