2. Academic Validation
  3. Design, synthesis and antiproliferative activity of a novel class of indole-2-carboxylate derivatives

Design, synthesis and antiproliferative activity of a novel class of indole-2-carboxylate derivatives

  • Eur J Med Chem. 2014 Aug 18:83:409-18. doi: 10.1016/j.ejmech.2014.05.043.
Xing-yue Ji 1,  Si-tu Xue 1,  Yue-chen Zhan 1,  Jia-jia Shen 1,  Lin-tao Wu 1,  Jie Jin 1,  Zhen Wang 2,  Zhuo-rong Li 3
Affiliations

Affiliations

  • 1 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
  • 2 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China. Electronic address: wangzhen@imb.pumc.edu.cn.
  • 3 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China. Electronic address: lizhuorong@imb.pumc.edu.cn.
PMID: 24996136 DOI: 10.1016/j.ejmech.2014.05.043
Abstract

Based on the chemical structure of Pyrroloquinoline quinone (PQQ), a novel class of indole-2-carboxylate derivatives was designed, synthesized and assayed for antiproliferative activity in Cancer cells in vitro. The biological results showed that some derivatives exhibited significant antiproliferative activity against HepG2, A549 and MCF7 cells. Notably, the novel compounds, methyl 6-amino-4-cyclohexylmethoxy-1H-indole-2-carboxylate (6e) and methyl 4-isopropoxy-6-methoxy-1H-indole-2-carboxylate (9l) exhibited more potent antiproliferative activity than the reference drugs PQQ and etoposide in vitro, with IC50 values ranging from 3.78 ± 0.58 to 24.08 ± 1.76 μM. Further biological assay showed that both compounds 6e and 9l increased ROS generation dose-dependently, and induced PARP cleavage in A549 cells. Consequently, 6e and 9l appeared as promising Anticancer lead compounds for further optimization.

Keywords

Antiproliferative activities; Indole-2-carboxylate derivatives; PQQ; ROS generation.

Figures