Excellent antitumor and antimetastatic activities based on novel coumarin/pyrazole oxime hybrids

  • Eur J Med Chem. 2019 Mar 15;166:470-479. doi: 10.1016/j.ejmech.2019.01.070.
Hong Dai  1 ,  Meiling Huang  1 ,  Jianqiang Qian  2 ,  Ji Liu  2 ,  Chi Meng  2 ,  Yangyang Li  2 ,  Guxu Ming  2 ,  Ting Zhang  2 ,  Senling Wang  3 ,  Yujun Shi  3 ,  Yong Yao  4 ,  Shushan Ge  1 ,  Yanan Zhang  5 ,  Yong Ling  6
Affiliations
  • 1. College of Chemistry and Chemical Engineering, Nantong University, Nantong, 226019, People's Republic of China; School of Pharmacy, Nantong University, Nantong, 226001, People's Republic of China.
  • 2. School of Pharmacy, Nantong University, Nantong, 226001, People's Republic of China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, People's Republic of China.
  • 3. College of Chemistry and Chemical Engineering, Nantong University, Nantong, 226019, People's Republic of China.
  • 4. College of Chemistry and Chemical Engineering, Nantong University, Nantong, 226019, People's Republic of China. Electronic address: [email protected].
  • 5. School of Pharmacy, Nantong University, Nantong, 226001, People's Republic of China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, People's Republic of China. Electronic address: [email protected].
  • 6. College of Chemistry and Chemical Engineering, Nantong University, Nantong, 226019, People's Republic of China; School of Pharmacy, Nantong University, Nantong, 226001, People's Republic of China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, People's Republic of China. Electronic address: [email protected].
PMID: 30739827 DOI: 10.1016/j.ejmech.2019.01.070
Abstract

A series of hybrids 10a-v based on coumarin/pyrazole oxime have been synthesized, and exhibit good to excellent antitumor activities. Compound 10n has shown remarkable Anticancer effect on SMMC-7721 cells (IC50 = 2.08 μM), which is considerably lower than 5-FU (IC50 = 37.8 μM) and similar to ADM (IC50 = 2.67 μM), with little effect on normal hepatic cells LO2. Notably, the suppression experiments of metastatic activities reveal that 10n also displays significant anti-metastasis effects through inhibiting cell migration and invasion in highly metastatic SMMC-7721 cell line, and dose-dependently reverses TGF-β1-induced epithelial-mesenchymal transition (EMT) procedure better than ADM. Finally, 10n also possesses low acute toxicity and potent tumor growth inhibitory property against SMMC-7721 cell lines in vivo. Our findings suggest that novel coumarin/pyrazole oxime hybrids are promising therapeutic agent candidates for further research.

Keywords
Antimetastasis; Antitumor activity; Coumarin; Hybrids; Pyrazole oxime.
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