Berberine derivatives with a long alkyl chain branched by hydroxyl group and methoxycarbonyl group at 9-position show improved anti-proliferation activity and membrane permeability in A549 cells

doi:10.1038/s41401-019-0346-1

	Berberine derivatives with a long alkyl chain branched by hydroxyl group and methoxycarbonyl group at 9-position show improved anti-proliferation activity and membrane permeability in A549 cells
	Liu, Yi 2; Zhu, Ke-xin 1,3; Cao, Lei 1; Xie, Zhi-fu 1; Gu, Min 1; Lu, Wei 2; Li, Jing-ya 1; Nan, Fa-jun 1
刊名	ACTA PHARMACOLOGICA SINICA
	2020-01-16
页码	12
关键词	berberine anticancer membrane permeability apoptosis mitochondria
ISSN号	1671-4083
DOI	10.1038/s41401-019-0346-1
通讯作者	Lu, Wei(wlu@chem.ecnu.edu.cn) ; Li, Jing-ya(jyli@simm.ac.cn) ; Nan, Fa-jun(fjnan@simm.ac.cn)
英文摘要	Berberine (BBR) exhibits diverse bioactivities, including anticancer activity; but its poor druggability limits its applications. In this study, we designed and synthesized a series of 9-O position modified BBR derivatives aiming to improve its cell permeability and anticancer activity, utilizing a long alkyl chain branched by hydroxyl group and methoxycarbonyl group. Among these compounds, B10 showed 3.6-fold higher intracellular concentration than BBR, as well as 60-fold increased anti-proliferation activity against human lung cancer A549 cells compared with BBR. Treatment with B10 (1, 2 mu M) induced apoptosis of A549 cells. Further investigations showed that B10 treatment dose-dependently affected mitochondrial functions, including oxygen consumption rate (OCR), mitochondrial membrane potential (MMP) and the morphology of mitochondria in A549 cells. Therefore, this work offers a new way for BBR structural modification through improving cell membrane permeability to affect mitochondrial functions and potential anti-tumor therapy in the future.
资助项目	Shanghai Commission of Science and Technology[16JC1405000] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040328] ; China Postdoctoral Science Foundation[2018M632186]
WOS关键词	IN-VITRO ; CANCER CELLS ; CYCLE ARREST ; CEREBRAL-ISCHEMIA ; DOWN-REGULATION ; APOPTOSIS ; PROLIFERATION ; MITOCHONDRIA ; PATHWAY ; REPERFUSION
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000508160500001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/282398]
专题	中国科学院上海药物研究所
通讯作者	Lu, Wei; Li, Jing-ya; Nan, Fa-jun
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Sch Chem & Mol Engn, Shanghai 200062, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Liu, Yi,Zhu, Ke-xin,Cao, Lei,et al. Berberine derivatives with a long alkyl chain branched by hydroxyl group and methoxycarbonyl group at 9-position show improved anti-proliferation activity and membrane permeability in A549 cells[J]. ACTA PHARMACOLOGICA SINICA,2020:12.
APA	Liu, Yi.,Zhu, Ke-xin.,Cao, Lei.,Xie, Zhi-fu.,Gu, Min.,...&Nan, Fa-jun.(2020).Berberine derivatives with a long alkyl chain branched by hydroxyl group and methoxycarbonyl group at 9-position show improved anti-proliferation activity and membrane permeability in A549 cells.ACTA PHARMACOLOGICA SINICA,12.
MLA	Liu, Yi,et al."Berberine derivatives with a long alkyl chain branched by hydroxyl group and methoxycarbonyl group at 9-position show improved anti-proliferation activity and membrane permeability in A549 cells".ACTA PHARMACOLOGICA SINICA (2020):12.