Pyrimidinyl-arylpropionic acid derivatives: viable resources in the development of new antineoplastic agents

doi:10.1007/s10637-009-9278-9

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Pyrimidinyl-arylpropionic acid derivatives: viable resources in the development of new antineoplastic agents
	Xiong, Xishan 1; Wang, Li 2; Ye, Yangliang3 ; Fu, Lili 1; Chen, Minli 4; Wang, Qingyi 1; Liu, Moyan 1; Tang, Jing 3; Dai, Bing 1; Shen, Jianhua3
刊名	INVESTIGATIONAL NEW DRUGS
	2010-08
卷号	28 期号:4 页码:472-481
关键词	Peroxisome proliferator-activated receptor gamma alpha-aryloxy-alpha-methylhydrocinnamic acid derivative IC50 Cell cycle Tumor
ISSN号	0167-6997
DOI	10.1007/s10637-009-9278-9
文献子类	Article
英文摘要	Numerous studies have documented that various naturally derived ligands or synthetic non-thiazolidinediones (TZD) as peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists have shown moderate or potent antitumor activities, which is PPAR gamma independent or partially dependent. However, the PPAR gamma agonistic or glucose-lowering activity is ranked first more often than antitumor activity to determine promising novel PPAR gamma agonists for potential clinical use. In this study, we hypothesized that there might exist some compounds with less PPAR gamma agonistic activity but potent antitumor activity. Thereafter, we evaluated the PPAR gamma agonistic and antitumor activity of a novel series of alpha-aryloxy-alpha-methylhydrocinnamic acid derivatives synthesized with the initial aim of developing novel PPAR gamma agonists as hypoglycemic agents. MTT assay results revealed that several compounds were able to inhibit cell proliferation in a dose-dependent manner with IC50 12.7-29.7 mu M, better than that of rosiglitazone (45.9-141 mu M), although the PPAR gamma agonistic activity of most compounds is much lower than rosiglitazone. Some compounds induced cell cycle arrest and apoptosis tested by Flow Cytometry. Oral administration of DH9 (100 mg/kg/d) for 21 days to BALB/c nude mice bearing xenografts including MGC-803, NCI-H460, HT-29 and OS-RC-2 cells significantly retarded tumor growth. DG8 and DJ5 showed benefits in some of the above four xenografts. Our findings demonstrate that these compounds have potent antitumor activity in vitro and in vivo and pyrimidinyl-arylpropionic acid derivatives might be viable resources in the development of new antineoplastic agents.
资助项目	National 863 Plan in High Technology Progress[2002AA2Z3130] ; National 863 Plan in High Technology Progress[2007AA02Z3Z1] ; Shanghai Leading Academic Discipline Project[B902]
WOS关键词	ACTIVATED-RECEPTOR-GAMMA ; PROSTATE-CANCER CELLS ; PPAR-ALPHA AGONISTS ; DUAL AGONISTS ; IN-VITRO ; APOPTOSIS ; ROSIGLITAZONE ; LIGANDS ; GROWTH ; DIFFERENTIATION
WOS研究方向	Oncology ; Pharmacology & Pharmacy
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000277942700011
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278813]
专题	药物发现与设计中心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	Mei, Changlin
作者单位	1.Second Mil Med Univ, Changzheng Hosp, Nephrol Inst PLA, Div Nephrol, Shanghai 200003, Peoples R China; 2.Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Div Nephrol, Shanghai 200011, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 4.Zhejiang Chinese Med Univ, Inst Lab Anim Resources, Hangzhou 310053, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Xiong, Xishan,Wang, Li,Ye, Yangliang,et al. Pyrimidinyl-arylpropionic acid derivatives: viable resources in the development of new antineoplastic agents[J]. INVESTIGATIONAL NEW DRUGS,2010,28(4):472-481.
APA	Xiong, Xishan.,Wang, Li.,Ye, Yangliang.,Fu, Lili.,Chen, Minli.,...&Mei, Changlin.(2010).Pyrimidinyl-arylpropionic acid derivatives: viable resources in the development of new antineoplastic agents.INVESTIGATIONAL NEW DRUGS,28(4),472-481.
MLA	Xiong, Xishan,et al."Pyrimidinyl-arylpropionic acid derivatives: viable resources in the development of new antineoplastic agents".INVESTIGATIONAL NEW DRUGS 28.4(2010):472-481.