Design and synthesis of C-10 modified and ring-truncated canthin-6-one analogues as effective membrane-active antibacterial agents

doi:10.1016/j.bmcl.2018.06.001

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	Design and synthesis of C-10 modified and ring-truncated canthin-6-one analogues as effective membrane-active antibacterial agents
	Dai, Jiangkun 2; Dan, Wenjia 2; Zhang, Yunyun 2; He, Mengfan 2; Wang, Junru 1,2
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2018-10-01
卷号	28 期号:18 页码:3123-3128
关键词	Canthin-6-one Synthesis Antibacterial activity Structure-activity relationships Mechanism
ISSN号	0960-894X
DOI	10.1016/j.bmcl.2018.06.001
文献子类	Article
英文摘要	A series of canthin-6-one analogues were designed and synthesized in order to study their antibacterial activity and structure-activity relationships. Compound 22 showed a broad spectrum of antibacterial activity and exhibited better bactericidal effect (8-fold superiorly against Staphylococcus aureus and 2-fold superiorly against Ralstonia solanacearum) than fosfomycin sodium and propineb with a minimum inhibitory concentration value of 2 mu g/mL. Moreover, it showed low cytotoxicity, stimulation on germination rates and good "drug-like" properties. Membrane-active mechanism was further studied by fluorescent microscopy, scanning electron microscopy, cytoplasmic beta-galactosidase leakage assay and evaluation of the molecular docking. The results showed that 22 may exert its bactericidal effect by damaging bacterial cell membranes and influencing the membrane formation, both of which could lead to cell death. The in vivo antibacterial assay with a protective efficacy of 68% demonstrated the potential of C ring-truncated canthin-6-one 22 as a new bactericide.
资助项目	National Natural Science Foundation of China[81773603] ; Open Foundation of Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education (Northwest University, China)[00000000] ; State Key Laboratory of Drug Research[SIMM1705KF-09]
WOS关键词	BETA-CARBOLINE ; DISCOVERY ; OPTIMIZATION ; ACID
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000442761400020
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279564]
专题	新药研究国家重点实验室中科院受体结构与功能重点实验室
通讯作者	Wang, Junru
作者单位	1.Chinese Acad Sci, Shanghai Inst Materia Med, State Key Lab Drug Res, 555 Zu Chong Zhi Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China 2.Northwest A&F Univ, Coll Chem & Pharm, 22 Xinong Rd, Yangling 712100, Shaanxi, Peoples R China;
推荐引用方式 GB/T 7714	Dai, Jiangkun,Dan, Wenjia,Zhang, Yunyun,et al. Design and synthesis of C-10 modified and ring-truncated canthin-6-one analogues as effective membrane-active antibacterial agents[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2018,28(18):3123-3128.
APA	Dai, Jiangkun,Dan, Wenjia,Zhang, Yunyun,He, Mengfan,&Wang, Junru.(2018).Design and synthesis of C-10 modified and ring-truncated canthin-6-one analogues as effective membrane-active antibacterial agents.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,28(18),3123-3128.
MLA	Dai, Jiangkun,et al."Design and synthesis of C-10 modified and ring-truncated canthin-6-one analogues as effective membrane-active antibacterial agents".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 28.18(2018):3123-3128.