Synthesis and Biological Activities of Novel Pleuromutilin Derivatives with a Substituted Thiadiazole Moiety as Potent Drug-Resistant Bacteria Inhibitors

doi:10.1021/jm500374c

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	Synthesis and Biological Activities of Novel Pleuromutilin Derivatives with a Substituted Thiadiazole Moiety as Potent Drug-Resistant Bacteria Inhibitors
	Xu, Ximing 4; Guo, Wenzhu 1; Zhang, Chao 1; Liu, Yu 1; Liang, Jianping 1; Xin, Zhijun3 ; Shang, Ruofeng 1; Pu, Xiuying 2
刊名	JOURNAL OF MEDICINAL CHEMISTRY
	2014-07-10
卷号	57 页码:5664-5678
ISSN号	0022-2623
DOI	10.1021/jm500374c
文献子类	Article
英文摘要	A series of novel pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae were tested by the agar dilution method and Oxford cup assay. The majority of the tested compounds displayed moderate antibacterial activities. Importantly, the three compounds with amino or tertiary amine groups in their side chains, 11, 13b, and 15c, were the most active antibacterial agents. Docking experiments carried out on the peptidyl transferase center (PTC) of 23S rRNA proved that there is a reasonable direct correlation between the binding free energy (Delta G(b), kcal/mol) and the antibacterial activity. Moreover, the pharmacokinetic profiles of 11 and 15c in rat were characterized by moderate clearance and oral bioavailability.
资助项目	"Five-Year" plan of national science and technology projects in rural areas[2011AA10A214]
WOS关键词	ANTIBACTERIAL ACTIVITY ; TIAMULIN ; CHEMISTRY ; ANTIBIOTICS ; VALNEMULIN ; DOCKING ; BINDING ; AGENTS ; FIT
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000338979100012
内容类型	期刊论文
源URL	[http://119.78.100.186/handle/113462/49885]
专题	近代物理研究所_重离子辐照药物研发中心
通讯作者	Liang, Jianping
作者单位	1.CAAS, Lanzhou Inst Husb & Pharmaceut Sci, Key Lab New Anim Drug Project Gansu Prov, Key Lab Vet Pharmaceut Dev,Minist Agr, Lanzhou 730050, Peoples R China 2.Lanzhou Univ Technol, Coll Life Sci & Engn, Lanzhou 730050, Peoples R China 3.Chinese Acad Sci, Inst Modern Phys, Lanzhou 730000, Peoples R China 4.Guiyang Med Univ, Sch Publ Hlth, Dept Toxicol, Guiyang 550004, Peoples R China
推荐引用方式 GB/T 7714	Xu, Ximing,Guo, Wenzhu,Zhang, Chao,et al. Synthesis and Biological Activities of Novel Pleuromutilin Derivatives with a Substituted Thiadiazole Moiety as Potent Drug-Resistant Bacteria Inhibitors[J]. JOURNAL OF MEDICINAL CHEMISTRY,2014,57:5664-5678.
APA	Xu, Ximing.,Guo, Wenzhu.,Zhang, Chao.,Liu, Yu.,Liang, Jianping.,...&Pu, Xiuying.(2014).Synthesis and Biological Activities of Novel Pleuromutilin Derivatives with a Substituted Thiadiazole Moiety as Potent Drug-Resistant Bacteria Inhibitors.JOURNAL OF MEDICINAL CHEMISTRY,57,5664-5678.
MLA	Xu, Ximing,et al."Synthesis and Biological Activities of Novel Pleuromutilin Derivatives with a Substituted Thiadiazole Moiety as Potent Drug-Resistant Bacteria Inhibitors".JOURNAL OF MEDICINAL CHEMISTRY 57(2014):5664-5678.