Unprecedented Citrinin Trimer Tricitinol B Functions as a Novel Topoisomerase II alpha Inhibitor

doi:10.1021/jm200511x

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	Unprecedented Citrinin Trimer Tricitinol B Functions as a Novel Topoisomerase II alpha Inhibitor
	Du, Lin 1; Liu, Hong-Chun2 ; Fu, Wei 3; Li, De-Hai 1; Pan, Qiu-Ming 2; Zhu, Tian-Jiao 1; Geng, Mei-Yu2 ; Gu, Qan-Qun 1
刊名	JOURNAL OF MEDICINAL CHEMISTRY
	2011-08-25
卷号	54 期号:16 页码:5796-5810
ISSN号	0022-2623
DOI	10.1021/jm200511x
文献子类	Article
英文摘要	Fifteen citrinin derivatives (1-4,6-16), including two unprecedented citrinin timers tricitrinols A (3) and B (4), were isolated from Penicillium citrinum HGY1-5. The six-membered ring A system is essential for the cytotoxicity of active dimers (1, 2, and 5) and trimers (3 and 4). Tricitrinol B (4) showed extensive cytotoxicity in 17 tumor cells with comparable low-micromolar IC50 values (1-10 mu M) and potential antimultidrug resistance capabilities. Tricitrinol B (4) induced cell apoptosis in HL60 and HCT116 cells via mainly extrinsic pathways and G2/M arrest. Further antitumor mechanism study and computational docking analysis indicated that tricitrinol B (4) works as an intercalating topoisomerase II alpha (topo II alpha) poison, which inhibits the enzyme activity of topo II alpha by interfering predominantly with the topo II alpha-mediated poststrand-passage deavage/religation equilibrium over with the prestrand-passage one and induced DNA damage. Tricitrinol B (4) represents a novel class of topo II alpha-inhibitory skeletons for developing new chemotherapeutic agents.
资助项目	Chinese National Science Fund[30973627] ; State Key Laboratory of Drug research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences[00000000] ; Natural Science Foundation of China for Distinguished Young Scholars[30725046] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09301-001] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09103-045] ; Program of Shanghai Subject Chief Scientist[10XD1405100] ; Science and Technology Planning Project of Shandong Province, China[2010GSF10216] ; Program for Changjiang Scholars and Innovative Research Team in University[IRT0944]
WOS关键词	FUNGUS ASPERGILLUS-GLAUCUS ; MOLECULAR-MECHANISMS ; PENICILLIUM-CITRINUM ; CANCER-CHEMOTHERAPY ; ANTICANCER DRUGS ; DNA CLEAVAGE ; SOLID-STATE ; APOPTOSIS ; DERIVATIVES ; TARGET
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000294077300013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278431]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Gu, Qan-Qun
作者单位	1.Ocean Univ China, Sch Med & Pharm, Minist Educ China, Key Lab Marine Drugs, Qingdao 266003, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China; 3.Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Du, Lin,Liu, Hong-Chun,Fu, Wei,et al. Unprecedented Citrinin Trimer Tricitinol B Functions as a Novel Topoisomerase II alpha Inhibitor[J]. JOURNAL OF MEDICINAL CHEMISTRY,2011,54(16):5796-5810.
APA	Du, Lin.,Liu, Hong-Chun.,Fu, Wei.,Li, De-Hai.,Pan, Qiu-Ming.,...&Gu, Qan-Qun.(2011).Unprecedented Citrinin Trimer Tricitinol B Functions as a Novel Topoisomerase II alpha Inhibitor.JOURNAL OF MEDICINAL CHEMISTRY,54(16),5796-5810.
MLA	Du, Lin,et al."Unprecedented Citrinin Trimer Tricitinol B Functions as a Novel Topoisomerase II alpha Inhibitor".JOURNAL OF MEDICINAL CHEMISTRY 54.16(2011):5796-5810.