Integration of multiscale molecular modeling approaches with the design and discovery of fusidic acid derivatives

doi:10.4155/fmc-2018-0567

	Integration of multiscale molecular modeling approaches with the design and discovery of fusidic acid derivatives
	Lu, Jing 1; Ni, Ling-Xuan 1; Wang, Jin-An 2; Liu, Ze-Yun 1; Shang, Kang-Le 1; Bi, Yi 1
刊名	FUTURE MEDICINAL CHEMISTRY
	2019-03-01
卷号	11 期号:12 页码:1427-1442
关键词	antibacterial activity docking fusidic acid half-life molecular dynamic simulation pharmacokinetics
ISSN号	1756-8919
DOI	10.4155/fmc-2018-0567
通讯作者	Lu, Jing(lujing_ytu@126.com) ; Bi, Yi(beeyee_413@163.com)
英文摘要	Aim: Fusidic acid (FA) is an effective antibiotic against Staphylococcus aureus, but it is metabolically unstable. Methods & results: 14 derivatives were designed and synthesized by blocking the metabolic sites of FA (21-COOH and 3-OH) to maintain antibacterial activity and prolong the half-life. Six derivatives showed good antibacterial activity, and the pharmacokinetic experiments confirmed that two derivatives modified in 21-COOH released FA in vivo and showed longer half-lives than FA. Docking analysis and structure-activity relationships indicated that the 3-glycine derivatives with more hydrogen-bonding acceptor sites and positively charged surface areas were more likely to have good antibacterial activity. Conclusion: The results suggest that introducing groups that block the metabolic sites of FA could maintain antibacterial activity and prolong the half-lives. [GRAPHICS] .
资助项目	Wellcome Trust (UK) ; University of Queensland (Australia) ; National Natural Science Foundation of China[81603024] ; National Natural Science Foundation of China[81773563] ; Project of Shandong Province Higher Educational Science and Technology Program[J16LM02] ; Taishan Scholar Project
WOS关键词	ELONGATION-FACTOR-G ; DYNAMICS ; RIBOSOME
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	FUTURE SCI LTD
WOS记录号	WOS:000484251900004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/288644]
专题	中国科学院上海药物研究所
通讯作者	Lu, Jing; Bi, Yi
作者单位	1.Yantai Univ, Sch Pharm, Key Lab Mol Pharmacol & Drug Evaluat, Minist Educ,Collaborat Innovat Ctr Adv Drug Deliv, Yantai 264005, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Lu, Jing,Ni, Ling-Xuan,Wang, Jin-An,et al. Integration of multiscale molecular modeling approaches with the design and discovery of fusidic acid derivatives[J]. FUTURE MEDICINAL CHEMISTRY,2019,11(12):1427-1442.
APA	Lu, Jing,Ni, Ling-Xuan,Wang, Jin-An,Liu, Ze-Yun,Shang, Kang-Le,&Bi, Yi.(2019).Integration of multiscale molecular modeling approaches with the design and discovery of fusidic acid derivatives.FUTURE MEDICINAL CHEMISTRY,11(12),1427-1442.
MLA	Lu, Jing,et al."Integration of multiscale molecular modeling approaches with the design and discovery of fusidic acid derivatives".FUTURE MEDICINAL CHEMISTRY 11.12(2019):1427-1442.