Synthesis and Biological Evaluation of Novel Uracil and 5-Fluorouracil-1-yl Acetic Acid-Colchicine Conjugate

doi:10.1007/s40242-015-4445-3

Chemical Research in Chinese Universities ›› 2015, Vol. 31 ›› Issue (3): 367-371.doi: 10.1007/s40242-015-4445-3

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Synthesis and Biological Evaluation of Novel Uracil and 5-Fluorouracil-1-yl Acetic Acid-Colchicine Conjugate

SHEN Lihong¹, HU Junping¹, WANG Haixian¹, WANG Aibing¹, LAI Yisheng², KANG Yanhui³

1. Handan Key Laboratory of Organic Small Molecule Materials, Handan College, Handan 056005, P. R. China;
2. Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, P. R. China;
3. Medical College of Hebei University of Engineering, Handan 056002, P. R. China

Received:2014-11-26 Revised:2015-03-20 Online:2015-06-01 Published:2015-03-30
Contact: SHEN Lihong E-mail:hdshenlihong@126.com
Supported by:
Supported by the Project of the Higher School Applied Technique Research Centre of Wild Plant Resources in Taihangshan Region of Hebei Province of China, the Higher School Science and Technology Projects of Hebei Province, China(No.Z2014131) and the Science Research Project of Handan College, China(No.14106).

Abstract

Abstract:

A series of novel uracil and 5-fluorouracil-1-yl-acetic acid-colchicine derivatives(6a-6n) was synthesized via coupling uracil and 5-fluorouracil(5-FU) with C-10 analogues of colchicine. The antitumor activities of the target compounds against human hepatocellular carcinoma(BEL7402) cells, human ovary carcinoma(A2780) cells, human lung adenocarcinoma(A549) cells and human breast carcinoma(MCF7) cells were tested in vitro, and the structure-activity relationship(SAR) of the compounds was also studied. The bioassay results demonstrate that most of the tested compounds display significant activity and particularly, compounds 6a, 6e, 6h and 6l show more potent cytotoxic activities than 5-fluorouracil and colchicine. The results show that the new derivatives of colchicine are potential suppressors on human cancer.

Key words: Colchicine, Uracil, 5-Fluorouracil, Antitumor activity

SHEN Lihong, HU Junping, WANG Haixian, WANG Aibing, LAI Yisheng, KANG Yanhui. Synthesis and Biological Evaluation of Novel Uracil and 5-Fluorouracil-1-yl Acetic Acid-Colchicine Conjugate[J]. Chemical Research in Chinese Universities, 2015, 31(3): 367-371.

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Synthesis and Biological Evaluation of Novel Uracil and 5-Fluorouracil-1-yl Acetic Acid-Colchicine Conjugate

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