Discovery, synthesis of novel fusidic acid derivatives possessed amino-terminal groups at the 3-hydroxyl position with anticancer activity

Jingxuan Ni, Mengqi Guo, Yucheng Cao, Lei Lei, Kangli Liu, Binghua Wang, Fangfang Lu, Rong G Zhai, Xiangwei Gao, Chunhong Yan, Hongbo Wang, Yi Bi

Research output: Contribution to journalArticle

Abstract

A series of novel fusidic acid (FA) derivatives were synthesized and screened for their in vitro cytotoxicity against the Hela, U87, KBV and MKN45 cancer cell lines. Selected FA derivatives with anti-tumor activity were firstly identified including compound 4, which exhibited good anti-proliferative activity with IC50 values in the range of 1.26–3.57 μM. Further research revealed that compound 4 induced Hela cells to undergo apoptosis by increasing the ratio of the cells in the Sub-G0/G1 phase via decreasing the neo-synthesized proteins in a dose-dependent manner from 1 to 10 μM. Compound 4 also showed good in vivo anti-tumor activity against the xenograft tumor of Hela cells and had no apparent toxicity. This study highlights the advantage of introducing the medium-length amino-terminal groups at the 3-OH position of FA to enhance its anti-tumor activity and suggests that compound 4 provides a starting point for designing more potent derivatives in the future.

LanguageEnglish (US)
Pages122-131
Number of pages10
JournalEuropean Journal of Medicinal Chemistry
Volume162
DOIs
StatePublished - Jan 15 2019

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Fusidic Acid
Hydroxyl Radical
Tumors
Apoptosis
Derivatives
Neoplasms
HeLa Cells
Cytotoxicity
Cell Cycle Resting Phase
Heterografts
Toxicity
G1 Phase
Cells
Inhibitory Concentration 50
Cell Line
Proteins
Research

Keywords

  • Anti-tumor activity
  • Apoptosis
  • Derivatives
  • Fusidic acid
  • Synthesis

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Discovery, synthesis of novel fusidic acid derivatives possessed amino-terminal groups at the 3-hydroxyl position with anticancer activity. / Ni, Jingxuan; Guo, Mengqi; Cao, Yucheng; Lei, Lei; Liu, Kangli; Wang, Binghua; Lu, Fangfang; Zhai, Rong G; Gao, Xiangwei; Yan, Chunhong; Wang, Hongbo; Bi, Yi.

In: European Journal of Medicinal Chemistry, Vol. 162, 15.01.2019, p. 122-131.

Research output: Contribution to journalArticle

Ni, Jingxuan ; Guo, Mengqi ; Cao, Yucheng ; Lei, Lei ; Liu, Kangli ; Wang, Binghua ; Lu, Fangfang ; Zhai, Rong G ; Gao, Xiangwei ; Yan, Chunhong ; Wang, Hongbo ; Bi, Yi. / Discovery, synthesis of novel fusidic acid derivatives possessed amino-terminal groups at the 3-hydroxyl position with anticancer activity. In: European Journal of Medicinal Chemistry. 2019 ; Vol. 162. pp. 122-131.
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