南方科技大学知识苑(SUSTech KC): Discovery and evolution of berberine analogues as anti<i>Helicobacter</i> pylori agents with multi-target mechanisms

题名	Discovery and evolution of berberine analogues as antiHelicobacter pylori agents with multi-target mechanisms
作者	Zhang, Xin 1; Wang, Genzhu 3; Kuang, Wenhua 5,6; Xu, Liting 5,6; He, Yuting 5,6; Zhou, Lirun 5,6; Zhang, Ying 5,6; Chen, Ruixing 5,6; Li, Huiying 2,5,6; Fan, Tianyun 2,5,6; Song, Yali 2; Wang, Jigang 2,4,5,6
通讯作者	Fan, Tianyun; Song, Yali; Wang, Jigang
发表日期	2024-10-01
DOI	10.1016/j.bioorg.2024.107628
发表期刊	BIOORGANIC CHEMISTRY 影响因子和分区
ISSN	0045-2068
EISSN	1090-2120
卷号	151
摘要	Thirty protoberberine derivatives, of which twenty five were new, were synthesized and evaluated for their antiHelicobacter pylori (HP) activities, taking 2,3,10-trimethoxy-9-p-methylbenzylaminoprotopalmatine chloride 1 as the lead. Among them, berberine (BBR) derivative 7c displayed the highest potency against six tested metronidazole (MTZ)-resistant strains and two tested MTZ-susceptible strains with the MIC values of 0.4-1.6 mu g/mL with favorable druglike profiles including low toxicity and high stabilities in plasma and artificial gastric fluid. Mechanistic study revealed that 7c might target HP urease with IC50 value of 0.27 mu g/mL against Jack bean urease. Furthermore, 7c might change the permeability of the bacterial membrane and direct interact with HP DNA, which also contribute to its bactericidal activity. Therefore, BBR derivatives constituted a new family of anti-HP candidates, with the advantage of good safety profile and multi-target mechanisms, and are worthy for further investigation.
关键词	Berberine analogues Helicobacter pylori Structure-activity relationship Urease DNA
相关链接	[来源记录]
收录类别	SCI
语种	英语
学校署名	通讯
资助项目	National Natural Science Foundation of China["82003575","82104013"] ; Natural Science Foundation of Bei- jing Municipality[7234407]
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Organic
WOS记录号	WOS:001273277200001
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
ESI学科分类	BIOLOGY & BIOCHEMISTRY
来源库	Web of Science
引用统计
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/789991
专题	南方科技大学第一附属医院
作者单位	1.Jining Med Univ, Affiliated Hosp, Dept Clin Pharm, Jining 272000, Shandong, Peoples R China 2.Southern Med Univ, Dongguan Maternal & Child Hlth Care Hosp, Postdoctoral Innovat Practice Base, Dongguan 523000, Guangdong, Peoples R China 3.Capital Med Univ, Elect Power Teaching Hosp, Dept Clin Pharm, Beijing 100073, Peoples R China 4.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Shenzhen Clin Res Ctr Geriatr,Dept Crit Med, Shenzhen 518020, Guangdong, Peoples R China 5.China Acad Chinese Med Sci, Artemisinin Res Ctr, State Key Lab Qual Ensurance & Sustainable Use Da, Beijing 100700, Peoples R China 6.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China
通讯作者单位	南方科技大学第一附属医院
推荐引用方式 GB/T 7714	Zhang, Xin,Wang, Genzhu,Kuang, Wenhua,et al. Discovery and evolution of berberine analogues as antiHelicobacter pylori agents with multi-target mechanisms[J]. BIOORGANIC CHEMISTRY,2024,151.
APA	Zhang, Xin.,Wang, Genzhu.,Kuang, Wenhua.,Xu, Liting.,He, Yuting.,...&Wang, Jigang.(2024).Discovery and evolution of berberine analogues as antiHelicobacter pylori agents with multi-target mechanisms.BIOORGANIC CHEMISTRY,151.
MLA	Zhang, Xin,et al."Discovery and evolution of berberine analogues as antiHelicobacter pylori agents with multi-target mechanisms".BIOORGANIC CHEMISTRY 151(2024).