Synthesis and Biological Evaluation of New Pleuromutilin Derivatives as Antibacterial Agents

Molecules

Ruo-Feng Shang²  Guan-Hua Wang⁴  Xi-Ming Xu¹  Si-Jie Liu³  Chao Zhang²  Yun-Peng Yi²  Jian-Ping Liang²  Yu Liu² 

[1]Department of Toxicology, School of Public Health, Guiyang Medical University, Guiyang 550004, China

[2] E-Mail:

[3]Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Ministry of Agriculture, Lanzhou 730050, China

[4] E-Mails:

[5]College of Chemical Engineering, Shijiazhuang University, Shijiazhuang 050035, China

[6] E-Mail:

[7]School of Public Health, Lanzhou University, Lanzhou 730000, China

[8] E-Mail:

关键词: pleuromutilin derivatives;    antibacterial activity;    synthesis;    molecular docking;    ADMET properties;   

DOI  :  10.3390/molecules191119050

来源: mdpi

【 摘 要 】

Several pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant S. aureus, methicillin-resistant S. epidermidis, S. aureus, S. epidermidis, E. coli, and B. cereus were tested by the agar dilution method and Oxford cup assay. All the screened compounds displayed potent activity. Compound 6d was the most active antibacterial agent because of its lowest MIC value and largest inhibition zone. Docking experiments were performed to understand the possible mode of the interactions between the derivatives and 50S ribosomal subunit. Moreover, the absorption, distribution, metabolism, excretion and toxicity properties of the synthesized compounds were analyzed after prediction using the Advanced Chemistry Development/Percepta Platform available online.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.