2. Academic Validation
  3. Synthesis and anti-proliferative activity of allogibberic acid derivatives containing 1,2,3-triazole pharmacophore

Synthesis and anti-proliferative activity of allogibberic acid derivatives containing 1,2,3-triazole pharmacophore

  • Bioorg Med Chem Lett. 2018 Aug 1;28(14):2543-2549. doi: 10.1016/j.bmcl.2018.05.038.
Ming-Jiang Wu 1,  Dong-Mei Wu 2,  Jing-Bo Chen 1,  Jing-Feng Zhao 1,  Liang Gong 3,  Ya-Xiao Gong 3,  Yan Li 4,  Xiao-Dong Yang 5,  Hongbin Zhang 6
Affiliations

Affiliations

  • 1 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China.
  • 2 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China; State Key Laboratory for Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Science, Kunming 650204, PR China.
  • 3 State Key Laboratory for Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Science, Kunming 650204, PR China.
  • 4 State Key Laboratory for Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Science, Kunming 650204, PR China. Electronic address: liyanb@mail.kib.ac.cn.
  • 5 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China. Electronic address: xdyang@ynu.edu.cn.
  • 6 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China. Electronic address: zhanghb@ynu.edu.cn.
PMID: 29884535 DOI: 10.1016/j.bmcl.2018.05.038
Abstract

Sixty novel allogibberic acid derivatives containing 1,2,3-triazole pharmacophore were designed and synthesized. The key chemical processes include aromatization of the A ring in Gibberellins, formation of allogibberic azides and its copper mediated Huisgen 1,3-dipolar cycloaddition with alkynes. A number of hybrids containing α,β-unsaturated ketone moiety exhibited excellent in vitro cytotoxic activities. Some of the hybrids were more selective to MCF-7 and SW480 cell lines with IC50 values at least 8-fold more cytotoxic than cisplatin (DDP). The most potent compounds C43 and C45 are more cytotoxic than cisplatin (DDP) against all tested five tumor cell lines, with IC50 values of 0.25-1.72 µM. Mechanism of action studies indicated that allogibberic-triazole derivative C45 could induce the S phase cell cycle arrest and Apoptosis in SMMC-7721 cell lines.

Keywords

1,2,3-Triazole; Allogibberic acid; Apoptosis; Cell cycle; Cytotoxic activity.

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