Synthesis, Crystal Structure, Antitumor Activity of Spiro-heterocyclic Mono-carbonyl Analogues of Curcumin

doi:10.6023/cjoc201402004

科研成果详情

题名	Synthesis, Crystal Structure, Antitumor Activity of Spiro-heterocyclic Mono-carbonyl Analogues of Curcumin
其他题名	Synthesis, Crystal Structure, Antitumor Activity of Spiro-heterocyclic Mono-carbonyl Analogues of Curcumin
作者	Wu, Jianzhang1; Weng, Bixia1; Qiu, Peihong 1; Cai, Zhijian 1,2; Fan, Lei 1; Ying, Shilong 1; Zhang, Xiuhua1,2; Wu, Xiaoping1,3; Liang, Guang1
发表日期	2014-08
发表期刊	CHINESE JOURNAL OF ORGANIC CHEMISTRY 影响因子和分区
语种	中文
原始文献类型	Article
关键词	mono-carbonyl analogs of curcumin spiro-heterocyclic antitumor synthesis
其他关键词	ENDOPLASMIC-RETICULUM STRESS ; CANCER ; APOPTOSIS ; DISCOVERY
摘要	To discover novel lead compounds with good antitumor activity and low toxicity, 14 spiroheterocycle mono-carbonyl analogs of curcumin (MCACs) were synthesized by 1,3-dipolar cycloaddition reaction. The one-pot reaction was carried out without catalyst, which showed the advantage of environmentally friendly. The structures of all compounds were characterized by BSI-MS, ESI-HRMS and H-1 NMR. The crystal structure of B6 was confirmed as monoclinic system by X-ray diffraction, which indicated high region-selectivity and stereo-selectivity in the reaction of these compounds. All compounds were screened for their abilities to inhibit the growth of human gastric cell SGC-7901, glioma cell U251, human large cell lung cancer cell lines NCI-H460 by thiazolyl blue tetrazolium bromide (MTT) assay, and some of them showed good antitumor activity. Among the active compounds, B1, B6, B7 and B11 exhibited strong antitumor efficacy on the three tumor cells and low cytotoxicity against human liver cells HL-7702. Both compounds B1 and B7 can significantly induce the activation of apoptosis related proteins cysteinyl aspartate specific proteinase (caspase3) and poly ADP-ribose polymerase (PARP), and induce the apoptosis of tumor cell. The synthesized spiro heterocycles derived from MCACs in this study were novel antitumor compounds, and these compounds appeared to possess good research prospect in the area of anti-tumor drugs.
其他摘要	To discover novel lead compounds with good antitumor activity and low toxicity, 14 spiroheterocycle mono-car-bonyl analogs of curcumin (MCACs) were synthesized by 1,3-dipolar cycloaddition reaction. The one-pot reaction was carried out without catalyst, which showed the advantage of environmentally friendly. The structures of all compounds were charac-terized by ESI-MS, ESI-HRMS and 1H NMR. The crystal structure of B6 was confirmed as monoclinic system by X-ray dif-fraction, which indicated high region-selectivity and stereo-selectivity in the reaction of these compounds. All compounds were screened for their abilities to inhibit the growth of human gastric cell SGC-7901, glioma cell U251, human large cell lung cancer cell lines NCI-H460 by thiazolyl blue tetrazolium bromide (MTT) assay, and some of them showed good antitumor activity. Among the active compounds, B1, B6, B7 and B11 exhibited strong antitumor efficacy on the three tumor cells and low cytotoxicity against human liver cells HL-7702. Both compounds B1 and B7 can significantly induce the activation of apoptosis related proteins cysteinyl aspartate specific proteinase (caspase3) and poly ADP-ribose polymerase (PARP), and induce the apoptosis of tumor cell. The synthesized spiro heterocycles derived from MCACs in this study were novel antitu-mor compounds, and these compounds appeared to possess good research prospect in the area of anti-tumor drugs.
资助项目	National Natural Science Fundation of ChinaNational Natural Science Foundation of China (NSFC) [81272462, 81102310]; Natural Science Fundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [LY12H30004, Y4090379]; Technology Foundation for Medical Science of Zhejiang Province [2012KYA129]; Wenzhou Sci-Tech Bureau [S20100045]; Zhejiang Provicial Project of Key Scientific Group [2010R50042-04]
出版者	SCIENCE PRESS
出版地	BEIJING
ISSN	0253-2786
卷号	34 期号:8 页码:1573-1581
DOI	10.6023/cjoc201402004
页数	9
WOS类目	Chemistry, Organic
WOS研究方向	Chemistry
WOS记录号	WOS:000341801900008
收录类别	SCIE ; SCOPUS ; CSCD ; 万方 ; PKU ; 北大核心 ; ISTIC ; SCI
学科领域	化学
URL	查看原文
CSCD记录号	CSCD:5226492
SCOPUSEID	2-s2.0-84907089981
通讯作者地址	[Wu, Xiaoping]Chemical Biology Research Center,College of Pharmaceutical Sciences,Wenzhou Medical Universtiy,Wenzhou,325035,China
Scopus学科分类	Organic Chemistry
万方分类号	R735.2(消化系肿瘤) ; R979.1(药品) ; R245.321(中医临床学)
引用统计	被引频次：2[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/3906
专题	药学院（分析测试中心）_生物有机与药物化学研究中心附属第一医院
通讯作者	Wu, Xiaoping
作者单位	1.Chemical Biology Research Center,College of Pharmaceutical Sciences,Wenzhou Medical Universtiy,Wenzhou,325035,China; 2.Department of Pharmacy,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 3.Institute of Tissue Transplantation and Immunology,Jinan University,Guangzhou,510632,China
第一作者单位	药学院（分析测试中心）_生物有机与药物化学研究中心
通讯作者单位	药学院（分析测试中心）_生物有机与药物化学研究中心
第一作者的第一单位	药学院（分析测试中心）_生物有机与药物化学研究中心
推荐引用方式 GB/T 7714	Wu, Jianzhang,Weng, Bixia,Qiu, Peihong,et al. Synthesis, Crystal Structure, Antitumor Activity of Spiro-heterocyclic Mono-carbonyl Analogues of Curcumin[J]. CHINESE JOURNAL OF ORGANIC CHEMISTRY,2014,34(8):1573-1581.
APA	Wu, Jianzhang., Weng, Bixia., Qiu, Peihong., Cai, Zhijian., Fan, Lei., ... & Liang, Guang. (2014). Synthesis, Crystal Structure, Antitumor Activity of Spiro-heterocyclic Mono-carbonyl Analogues of Curcumin. CHINESE JOURNAL OF ORGANIC CHEMISTRY, 34(8), 1573-1581.
MLA	Wu, Jianzhang,et al."Synthesis, Crystal Structure, Antitumor Activity of Spiro-heterocyclic Mono-carbonyl Analogues of Curcumin".CHINESE JOURNAL OF ORGANIC CHEMISTRY 34.8(2014):1573-1581.

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