Discovery of novel inhibitors of Streptococcus pneumoniae based on the virtual screening with the homology-modeled structure of histidine kinase (VicK)

doi:10.1186/1471-2180-9-129

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Discovery of novel inhibitors of Streptococcus pneumoniae based on the virtual screening with the homology-modeled structure of histidine kinase (VicK)
	Li, Nan 2; Wang, Fei 1; Niu, Siqiang 2; Cao, Ju 2; Wu, Kaifeng 2; Li, Youqiang 2; Yin, Nanlin 2; Zhang, Xuemei 2; Zhu, Weiliang1 ; Yin, Yibing 2
刊名	BMC MICROBIOLOGY
	2009-06-27
卷号	9
ISSN号	1471-2180
DOI	10.1186/1471-2180-9-129
文献子类	Article
英文摘要	Background: Due to the widespread abusage of antibiotics, antibiotic-resistance in Streptococcus pneumoniae (S. pneumoniae) has been increasing quickly in recent years, and it is obviously urgent to develop new types of antibiotics. Two-component systems (TCSs) are the major signal transduction pathways in bacteria and have emerged as potential targets for antibacterial drugs. Among the 13 pairs of TCSs proteins presenting in S. pneumoniae, VicR/K is the unique one essential for bacterium growth, and block agents to which, if can be found, may be developed as effective antibiotics against S. pneumoniae infection. Results: Using a structure-based virtual screening (SBVS) method, 105 compounds were computationally identified as potential inhibitors of the histidine kinase (HK) VicK protein from the compound library SPECS. Six of them were then validated in vitro to be active in inhibiting the growth of S. pneumoniae without obvious cytotoxicity to Vero cell. In mouse sepsis models, these compounds are still able to decrease the mortality of the mice infected by S. pneumoniae and one compound even has significant therapeutic effect. Conclusion: To our knowledge, these compounds are the first reported inhibitors of HK with antibacterial activity in vitro and in vivo, and are novel lead structures for developing new drugs to combat pneumococcal infection.
资助项目	National Natural Science Foundation of China[30671868] ; National Natural Science Foundation of China[20721003]
WOS关键词	2-COMPONENT SIGNAL-TRANSDUCTION ; YYCF RESPONSE-REGULATOR ; STAPHYLOCOCCUS-AUREUS ; GENOMIC ANALYSIS ; ANTIINFECTIVE THERAPY ; BACILLUS-SUBTILIS ; SYSTEM ; VIRULENCE ; DOMAIN ; INFECTIONS
WOS研究方向	Microbiology
语种	英语
出版者	BMC
WOS记录号	WOS:000268668400001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279206]
专题	药物发现与设计中心
通讯作者	Yin, Yibing
作者单位	1.Chinese Acad Sci, Grad Sch, Shanghai Inst Mat Med, Drug Discovery & Design Ctr,State Key Lab Drug Re, Shanghai 201203, Peoples R China 2.Chongqing Med Univ, Key Lab Lab Med Diagnost, Minist Educ, Fac Lab Med, Chongqing 400016, Peoples R China;
推荐引用方式 GB/T 7714	Li, Nan,Wang, Fei,Niu, Siqiang,et al. Discovery of novel inhibitors of Streptococcus pneumoniae based on the virtual screening with the homology-modeled structure of histidine kinase (VicK)[J]. BMC MICROBIOLOGY,2009,9.
APA	Li, Nan.,Wang, Fei.,Niu, Siqiang.,Cao, Ju.,Wu, Kaifeng.,...&Yin, Yibing.(2009).Discovery of novel inhibitors of Streptococcus pneumoniae based on the virtual screening with the homology-modeled structure of histidine kinase (VicK).BMC MICROBIOLOGY,9.
MLA	Li, Nan,et al."Discovery of novel inhibitors of Streptococcus pneumoniae based on the virtual screening with the homology-modeled structure of histidine kinase (VicK)".BMC MICROBIOLOGY 9(2009).