Synthesis of novel pleuromutilin derivatives. Part 1: preliminary studies of antituberculosis activity.
The worldwide threat from tuberculosis (TB) has resulted in great demand for new drugs, particularly those that can treat multidrug-resistant TB. We synthesized novel pleuromutilin derivatives with N-benzylamine side chain substituted at the C14 position and evaluated their activity in vitro against a virulent strain of Mycobacterium tuberculosis (H37Rv). The primary assay results showed that five compounds inhibited the H37Rv at 20μM, with a MIC of one of the analogues as low as 7.2μM.
Department of Applied Chemistry and Pharmaceuticals, Beijing Institute of Technology, Beijing 100081, PR China.
Ying-Jie
YJ
Dong
Department of Applied Chemistry and Pharmaceuticals, Beijing Institute of Technology, Beijing 100081, PR China.
Zi-Hui
ZH
Meng
Department of Applied Chemistry and Pharmaceuticals, Beijing Institute of Technology, Beijing 100081, PR China.
Yan-Qing
YQ
Mi
Department of Applied Chemistry and Pharmaceuticals, Beijing Institute of Technology, Beijing 100081, PR China.
Chun
C
Zhang
Department of Applied Chemistry and Pharmaceuticals, Beijing Institute of Technology, Beijing 100081, PR China.
Zhi-Hao
ZH
Cui
Department of Applied Chemistry and Pharmaceuticals, Beijing Institute of Technology, Beijing 100081, PR China.
Peng
P
Wang
Department of Applied Chemistry and Pharmaceuticals, Beijing Institute of Technology, Beijing 100081, PR China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China. Electronic address: zbxu@bit.edu.cn.
Zhi-Bin
ZB
Xu
D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004352:Drug Resistance, Microbial; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011083:Polycyclic Compounds; D013329:Structure-Activity Relationship; D000097567:Pleuromutilins
D000995:Antitubercular Agents; D004224:Diterpenes; D011083:Polycyclic Compounds; D000097567:Pleuromutilins
Antitubercular activity; N-Benzylamine side chain; Pleuromutilin derivatives