2. Academic Validation
  3. Synthesis, antitumor activity evaluation and mechanistic study of novel hederacolchiside A1 derivatives bearing an aryl triazole moiety

Synthesis, antitumor activity evaluation and mechanistic study of novel hederacolchiside A1 derivatives bearing an aryl triazole moiety

  • Bioorg Med Chem. 2018 Aug 7;26(14):4025-4033. doi: 10.1016/j.bmc.2018.06.026.
Hui-Ning Li 1,  Hui Wang 2,  Zhi-Peng Wang 1,  Hai-Ning Yan 1,  Miao Zhang 1,  Yang Liu 3,  Mao-Sheng Cheng 4
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 2 Key Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China; Shanghai Green Valley (Benxi) Pharmaceutical Co. Ltd., Benxi 117004, China.
  • 3 Key Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: y.liu@syphu.edu.cn.
  • 4 Key Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: mscheng@syphu.edu.cn.
PMID: 29958763 DOI: 10.1016/j.bmc.2018.06.026
Abstract

In an attempt to arrive at a more potent antitumor agent than the parent natural saponin hederacolchiside A1, 23 hederacolchiside A1 derivatives (4a-4w) were synthesized via Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition and screened in vitro for cytotoxicity against six human Cancer cell lines. The structure-activity relationship of these compounds was elucidated, and the biological screening results showed that most of the compounds exhibited moderate to high levels of antitumor activities against the tested cell lines and some of them displayed more potent inhibitory activities compared with hederacolchiside A1. Compound 4f showed a 2- to 7-fold more potent activity than hederacolchiside A1. The mechanistic study of 4f revealed that this compound can induce cell Apoptosis in HepG2 cells via mitochondrial-mediated intrinsic pathways.

Keywords

Antitumor activity; Apoptosis; Hederacolchiside A(1); Saponin; Structure-activity relationship.

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