数字农科院2.0

Discovery of novel thiazole-pleuromutilin derivatives with potent antibacterial activity

文献类型： 外文期刊

作者： Xian Long Qi;He Chao Zhang;Xiao Xu;Xi Wang Liu;Ya Jun Yang;Zhun Li;Jian Yong Li

作者机构：

关键词： Antibacterial activity;Pleuromutilin derivatives;Synthesis;Thiazole;Toxicity

期刊名称： European Journal of Medicinal Chemistry

ISSN： 0223-5234

年卷期： 2025 年 287 卷

页码：

收录情况： SCIE（2025版）

摘要： A series of novel thiazole-pleuromutilin derivatives were designed and synthesized, and their antibacterial activities were evaluated. Most of the synthesized derivatives showed good activity against Gram-positive bacteria, among which compound h19 was more prominent and had the strongest antibacterial activity against MRSA. Compound h19 was selected for further evaluation of bacterial time-kill kinetics, and the results demonstrated its highly promising efficacy in inhibiting MRSA growth. Moreover, h19 exhibited a superior post-antibiotic effect (PAE) value and a lower possibility for bacterial resistance development compared to tiamulin. Docking studies demonstrated the strong affinity of h19 for the 50S ribosomal subunit with a binding free energy of −10.6 kcal/mol. The cytotoxic assay indicated that h19 had low cytotoxicity on both HEK293T and HepG2 cells (IC50 > 200 μM). In MRSA systemic-infected mouse model, h19 improved survival rates, reduced the bacterial load, and alleviated pathological changes in the lungs of the infected mice, which exhibited a more potent antibacterial efficacy compared to tiamulin. Compound h19 also displayed low oral toxicity with an LD50 value more than 2000 mg/kg.

分类号：

  • 相关文献

[1]Synthesis and evaluation of novel pleuromutilin derivatives targeting the 50S ribosomal subunit for antibacterial ability. Qinqin Liu,Hongjuan Zhang,Yun Peng Yi,Panpan Wang,Wanxia Pu,Shengyi Wang,Ruofeng Shang. 2023

[2]Discovery of novel pleuromutilin derivatives as potent antibacterial agents. Yuhang Zhou,Yunpeng Yi,Jiangkun Wang,Zheng Yang,Qinqin Liu,Wanxia Pu,Ruofeng Shang. 2022

[3]Novel pyridinium cationic pleuromutilin analogues overcoming bacterial multidrug resistance. Yunpeng Yi,Jiaming Zhang,Jiakun Zuo,Maolu Zhang,Shifa Yang,Zhongli Huang,Guiyu Li,Ruofeng Shang,Shuqian Lin. 2023

[4]Design, synthesis, and biological evaluation of novel pleuromutilin derivatives with methicillin-resistant Staphylococcus aureus -targeting phenol linker groups. Yi, Yunpeng,Zhang, Jiaming,Lin, Shuqian,Wang, Haiting,Li, Guiyu,Yang, Shifa,Shang, Ruofeng,Zhang, Rongling,Li, Fei. 2025

[5]Synthesis and Antibacterial Activity of Novel Pleuromutilin Derivatives. Liu, Huixian,Xiao, Sui,Zhang, Lifang,Wang, Xiaoyang,Xue, Feiqun,Zhang, Depeng,Mu, Shuhua.

[6]Synthesis and antibacterial activities of 1-substituted aryl-4-ethoxycarbonyi-5-acylamino-1,2,3-triszoles. Chen, MD,Lu, SJ,Yang, YH,Du, XL,Yuan, GP,Yang, SY. 2001

[7]Synthesis and antibacterial evaluation of novel pleuromutilin derivatives. Shang, Ruofeng,Liu, Yu,Guo, Wenzhu,Guo, Zhiting,Hao, Baocheng,Liang Jianping,Xin, Zhijun.

[8]Synthesis, Antimicrobial Activities, and Model of Action of Indolyl Derivatives Containing Amino-Guanidinium Moieties. Yu Xi Li,Xiang Geng,Qi Tao,Ruo Chen Hao,Ya Jun Yang,Xi Wang Liu,Jian Yong Li. 2025

[9]Synthesis, Antimicrobial Activities, and Model of Action of Novel Tetralone Derivatives Containing Aminoguanidinium Moiety. Qing Jie Zhang,Yu Xi Li,Wen Bo Ge,Li Xia Bai,Xiao Xu,Ya Jun Yang,Xi Wang Liu,Jian Yong Li. 2025

[10]Synthesis of aspirin eugenol ester and its biological activity. Li, Jian-yong,Yu, Yuan-guang,Wang, Qi-wen,Zhang, Ji-yu,Yang, Ya-jun,Li, Bing,Zhou, Xu-zheng,Niu, Jian-rong,Wei, Xiao-juan,Liu, Xi-wang,Liu, Zhi-qi.

[11]Molecular design, synthesis and bioactivity of glycosyl hydrazine and hydrazone derivatives: Notable effects of the sugar moiety. Cui, Zining,Dohi, Hirofumi,Nishida, Yoshihiro,Cui, Zining,Yang, Xinling,Shi, Yanxia,Uzawa, Hirotaka,Cui, Jingrong. 2011

[12]Synthesis and biological activity evaluation of a novel pleuromutilin derivative 22-((2-methyl-1-(1H-pyrrole-2-carboxamido)propan-2-yl)thio)-deoxypleuromutilin. Zhun Li,Danqian Ma,Chang Liu,Zhe Qin,Lixia Bai,Wenbo Ge,Xiao Xu,Jianyong Li. 2025

[13]Design, synthesis, and bioactivity of newly potent pleuromutilin derivatives. Zhun Li,Danqian Ma,Chang Liu,Xianlong Qi,Zhe Qin,Yajun Yang,Jianyong Li. 2025

[14]植物甾醇脂肪酸酯的功效和合成方法的研究进展(英文). 王明霞,黄沁洁,王江薇,黄凤洪. 2007

[15]Synthesis And Biological Activity Evaluation O.f Novel Heterocyclic Pleuromutilin D erivatives. Qin, Wenwen,Shang, Ruofeng,Yi, Yunpeng,Liu, Yu,Dong, Pengcheng,Fu, Yunxing,Liang, Jiangping. 2017

[16]Synthesis And Antibacterial Activities Of N.ovel Pleuromutilin Derivatives With A Substituted Pyrimidine Moiety. Liang, Jianping,Huang, Xin,Yi, Yunpeng,Yi, Yunpeng,Shang, Ruofeng,Liu, Yu,Huang, Xin,Xu, Ximing,Xu, Shuijin,Shang, Ruofeng,Liu, Yu,Liang, Jianping. 2017

[17]Design, synthesis and antibacterial activity evaluation of pleuromutilin derivatives according to twin drug theory. Liu, Hui-Xian,Cui, Ge,Ma, Dong-Lai,Zhang, Yue,Xue, Fei-Qun. 2021

[18]Novel pleuromutilin derivatives conjugated with phenyl-sulfide and boron-containing moieties as potent antibacterial agents against antibiotic-resistant bacteria. Xinyu Luo,Guangxu Wu,Jing Feng,Jie Zhang,Hengjian Fu,Hang Yu,Zunsheng Han,Wansen Nie,Zihao Zhu,Bo Liu,Weidong Pan,Beibei Li,Yan Wang,Chi Zhang,Tianlei Li,Wenxuan Zhang,Song Wu. 2024

[19]A Facile Synthesis of DNA-Magnetic-Fluorescent Composite Particles. Wang, Miao,Xu, Siyuan,She, Yongxin,Jin, Maojun,Jin, Fen,Shao, Hua,Wang, Jing,Wang, Miao,Xu, Siyuan,She, Yongxin,Jin, Maojun,Jin, Fen,Shao, Hua,Wang, Jing,Wang, Miao,Xu, Siyuan,She, Yongxin,Jin, Maojun,Jin, Fen,Shao, Hua,Wang, Jing. 2012

[20]Synthesis and In Vitro Anticancer Activity of Novel 2-((3-thioureido)carbonyl)phenyl Acetate Derivatives. Xiong, Lin,Gao, Ya-Qin,Niu, Chu-E,Wang, Hong-Bo,Li, Wei-Hong,Xiong, Lin,Gao, Ya-Qin,Niu, Chu-E,Wang, Hong-Bo,Li, Wei-Hong. 2014

作者其他论文 更多>>