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

doi:10.6023/cjoc201402004

Chin. J. Org. Chem. ›› 2014, Vol. 34 ›› Issue (8): 1573-1581.DOI: 10.6023/cjoc201402004 Previous Articles Next Articles

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螺杂环单羰基姜黄素类似物的合成、晶体结构与抗肿瘤活性研究

吴建章^a, 翁碧霞^a, 仇佩虹^a, 蔡志坚^a,b, 范蕾^a, 应士龙^a, 张秀华^a,b, 吴晓萍^a,c, 梁广^a

a 温州医科大学药学院化学生物学研究中心温州 325035;
b 温州医科大学附属第一医院药剂科温州 325000;
c 暨南大学组织移植与免疫实验中心广州 510632

收稿日期:2014-02-05 修回日期:2014-04-05 发布日期:2014-05-05
通讯作者: 张秀华，吴晓萍 E-mail:wjzwzmc@126.com,wujianzhang6@163.com
基金资助:
国家自然科学基金（Nos.81272462，81102310）、浙江省自然科学基金（Nos.LY12H30004，Y4090379）、浙江省医药卫生科技计划（No.2012KYA129）、温州市科技局（No.S20100045）、浙江省重点科技创新团队（Nos.2010R50042-04）资助项目

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

Wu Jianzhang^a, Weng Bixia^a, Qiu Peihong^a, Cai Zhijian^a,b, Fan Lei^a, Ying Shilong^a, Zhang Xiuhua^a,b, Wu Xiaoping^a,c, Liang Guang^a

a Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou 325035;
b Department of Pharmacy, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000;
b Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632

Received:2014-02-05 Revised:2014-04-05 Published:2014-05-05
Supported by:
Project supported by the National Natural Science Fundation of China (Nos. 81272462, 81102310), the Natural Science Fundation of Zhejiang Province (Nos. LY12H30004, Y4090379), the Technology Foundation for Medical Science of Zhejiang Province (No. 2012KYA129), the Project of Wenzhou Sci-Tech Bureau (No. S20100045), the Zhejiang Provicial Project of Key Scientific Group (No. 2010R50042-04).

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 characterized by ESI-MS, ESI-HRMS and ¹H 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.

Key words: mono-carbonyl analogs of curcumin, spiro-heterocyclic, antitumor, synthesis

Cite this article

Wu Jianzhang, Weng Bixia, Qiu Peihong, Cai Zhijian, Fan Lei, Ying Shilong, Zhang Xiuhua, Wu Xiaoping, Liang Guang. Synthesis, Crystal Structure, Antitumor Activity of Spiro-heterocyclic Mono-carbonyl Analogues of Curcumin[J]. Chin. J. Org. Chem., 2014, 34(8): 1573-1581.

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螺杂环单羰基姜黄素类似物的合成、晶体结构与抗肿瘤活性研究

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

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