Synthesis and Antitumor Activities of Novel Bivalent 1-Heterocyclic-β-carbolines Linked by Alkylamino Spacer

doi:10.6023/cjoc201701005

Chin. J. Org. Chem. ›› 2017, Vol. 37 ›› Issue (7): 1741-1747.DOI: 10.6023/cjoc201701005 Previous Articles Next Articles

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双-(1-杂环-β-咔啉)-3-烷氨基衍生物的合成与抗肿瘤活性

郭亮^a,b, 谢建伟^a,b, 范文玺^c, 陈伟^c, 代斌^a,b, 马芹^c

a. 石河子大学化学化工学院石河子 832003;
b. 新疆兵团化工绿色过程重点实验室石河子 832003;
c. 新疆华世丹药物研究有限责任公司乌鲁木齐 830011

收稿日期:2017-01-04 修回日期:2017-03-07 发布日期:2017-03-17
通讯作者: 代斌 E-mail:db_tea@shzu.edu.cn
基金资助:
新疆维吾尔自治区青年科技创新人才培养工程（No.qn2015jc067）资助项目

Synthesis and Antitumor Activities of Novel Bivalent 1-Heterocyclic-β-carbolines Linked by Alkylamino Spacer

Guo Liang^a,b, Xie Jianwei^a,b, Fan Wenxi^c, Chen Wei^c, Dai Bin^a,b, Ma Qin^c

a. School of Chemistry and Chemical Engineering, Shihezi University, Shihezi 832003;
b. Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi 832003;
c. Xinjiang Huashidan Pharmaceutical Research Co., Ltd., Urumqi 830011

Received:2017-01-04 Revised:2017-03-07 Published:2017-03-17
Contact: 10.6023/cjoc201701005 E-mail:db_tea@shzu.edu.cn
Supported by:
Project supported by the Program for Outstanding Youth Science and Technology Innovation Talents Training in Xinjiang Uygur Autonomous Region (No.qn2015jc067).

1. Synthesis and Antitumor Activities of Novel Bivalent 1-Heterocyclic-β-carbolines Linked by Alkylamino Spacer.PDF(1278KB)

Abstract

In order to find novel antitumor candidate compounds with high efficiency and low toxicity, a series of 1-heterocyclic substituted bivalent β-carbolines with a spacer of four or five methylene units between the two 3-methylamino group were synthesized, and the chemical structures were characterized by ¹H NMR, ¹³C NMR, and HRMS. The cytotoxic activities of all bivalent β-carbolines were evaluated in vitro against a panel of human tumor cell lines (22RV1, SK-OV-3, MCF-7, LLC, Eca-109, BGC-823, HT-29, HepG-2, A375, and 769-P) and compared with the positive control cisplatin and monovalent β-carbolines. The results demonstrated that compounds 5a~5h exhibited potent cytotoxic activities with IC₅₀ values lower than 10 μmol·L^-1. In particular, compounds 5d and 5h, both of which had a spacer of five methylene units, exhibited significant inhibitory activity against 769-P and 22RV1 with IC₅₀ values of 0.8 μmol·L^-1 and 0.6 μmol·L^-1, respectively.

Key words: bivalent β-carboline, synthesis, antitumor activity, structure-activity relationship

Cite this article

Guo Liang, Xie Jianwei, Fan Wenxi, Chen Wei, Dai Bin, Ma Qin. Synthesis and Antitumor Activities of Novel Bivalent 1-Heterocyclic-β-carbolines Linked by Alkylamino Spacer[J]. Chin. J. Org. Chem., 2017, 37(7): 1741-1747.

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双-(1-杂环-β-咔啉)-3-烷氨基衍生物的合成与抗肿瘤活性

Synthesis and Antitumor Activities of Novel Bivalent 1-Heterocyclic-β-carbolines Linked by Alkylamino Spacer

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