2. Academic Validation
  3. Novel dihydropyrazole-chromen: Design and modulates hTERT inhibition proliferation of MGC-803

Novel dihydropyrazole-chromen: Design and modulates hTERT inhibition proliferation of MGC-803

  • Eur J Med Chem. 2016 Mar 3:110:65-75. doi: 10.1016/j.ejmech.2016.01.014.
Yan Yan Chen 1,  Xiao Qin Wu 2,  Wen Jian Tang 2,  Jing Bo Shi 2,  Jun Li 3,  Xin Hua Liu 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Anhui Medical University, Hefei, 230032, PR China; The Fourth Affiliated Hospital of Anhui Medical University, Hefei, 230022, PR China.
  • 2 School of Pharmacy, Anhui Medical University, Hefei, 230032, PR China.
  • 3 School of Pharmacy, Anhui Medical University, Hefei, 230032, PR China. Electronic address: lijun@ahmu.edu.cn.
  • 4 School of Pharmacy, Anhui Medical University, Hefei, 230032, PR China. Electronic address: xhliuhx@163.com.
PMID: 26807545 DOI: 10.1016/j.ejmech.2016.01.014
Abstract

Dominant-negative mutant of Telomerase hTERT was demonstrated to show selective Anticancer effects in tumor cells. But, an effective hTERT inhibitor with high selectivity has not been developed so far. Focused on hTERT, a novel dihydropyrazole-chromen (13k) controlling hTERT was designed. Title compound 13k occupied high antiproliferative activity against MGC-803 cells with IC50 value 1.41 μM, but it manifested obvious un-toxic effect on human normal gastric mucosa cells with the IC50 2.3 mM. Treated with compound 13k, the further inhibition mechanisms by modulating hTERT was explored, the results showed that expression of hTERT was clearly modulated, and then β-catenin activation was decreased, thereby the expression of downstream signaling molecules including c-Myc and cyclin D1 was modulated, leading to inhibition MGC-803 cells proliferation.

Keywords

Dihydropyrazole-chromen; Selective anticancer activity; TERT modulator; Telomerase.

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