2. Academic Validation
  3. Click chemistry-based synthesis and anticancer activity evaluation of novel C-14 1,2,3-triazole dehydroabietic acid hybrids

Click chemistry-based synthesis and anticancer activity evaluation of novel C-14 1,2,3-triazole dehydroabietic acid hybrids

  • Eur J Med Chem. 2017 Sep 29:138:1042-1052. doi: 10.1016/j.ejmech.2017.07.049.
Wei Hou 1,  Zhi Luo 2,  Guanjun Zhang 3,  Danhui Cao 1,  Di Li 1,  Haoqiang Ruan 1,  Benfang Helen Ruan 1,  Lin Su 4,  Hongtao Xu 5
Affiliations

Affiliations

  • 1 College of Pharmaceutical Science, Collaborative Innovation Center of Yangtza River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, PR China.
  • 2 Shanghai Evergene Biotech Co,. Ltd., Shanghai 201499, PR China.
  • 3 College of Chemical Engineering and Materials Science, Tianjin University of Science & Technology, Tianjin 300457, PR China.
  • 4 College of Pharmaceutical Science, Collaborative Innovation Center of Yangtza River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, PR China. Electronic address: sulin8023@zjut.edu.cn.
  • 5 Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, PR China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address: xuhongtao2010@126.com.
PMID: 28759877 DOI: 10.1016/j.ejmech.2017.07.049
Abstract

A concise and efficient synthetic approach has been established to readily access a series of novel C-14 1,2,3-triazole-tethered dehydroabietic acid derivatives in moderate to high yields. In vitro antiproliferative activity evaluation indicated that most of the hybrids exhibited potent inhibitory activities in a variety of Cancer cell lines with low micromolar to submicromolar IC50 values. Further studies demonstrated that some of these analogues such as 20, 21, and 24 were also effective against adriamycin-resistant MCF-7 clone at low concentrations in a dose-dependent manner. Notably, the most potent compound 24, which possesses a 3-(tert-butoxycarbonylamino)phenyl-substituted triazole moiety, not only exhibited obviously improved IC50 values ranging from 0.7 to 1.2 μM against a panel of tested Cancer cells, but also showed very weak cytotoxicity on normal cells. Preliminary mechanism studies indicated that compound 24 could induce Apoptosis in MDA-MB-231 cells and was worth developing into a novel natural product-like Anticancer lead by proper structure modification.

Keywords

1,2,3-triazole; Cancer; Click chemistry; Dehydroabietic acid; Drug resistance; Synthesis; Terpenoids.

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