2. Academic Validation
  3. Design, synthesis and biological evaluation of novel 1,2,4-triazolo [3,4-b][1,3,4] thiadiazines bearing furan and thiophene nucleus

Design, synthesis and biological evaluation of novel 1,2,4-triazolo [3,4-b][1,3,4] thiadiazines bearing furan and thiophene nucleus

  • Eur J Med Chem. 2015 Oct 20:103:335-42. doi: 10.1016/j.ejmech.2015.08.053.
Bei Zhang 1,  Yan-Hong Li 1,  Yang Liu 1,  Yu-Rong Chen 1,  En-Shan Pan 2,  Wen-Wei You 3,  Pei-Liang Zhao 4
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
  • 2 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China.
  • 3 Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: youww@smu.edu.cn.
  • 4 Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: plzhao@smu.edu.cn.
PMID: 26363869 DOI: 10.1016/j.ejmech.2015.08.053
Abstract

Twenty-six novel 1,2,4-triazolo [3,4-b][1,3,4] thiadiazines containing furan and thiophene nucleus were designed, synthesized and evaluated for their antiproliferative activities. The results indicated that most of the compounds showed moderate to potent antiproliferative activities against four Cancer cell lines, PC-3, HepG2, A549, and MCF-7. Particularly, compound 32 showed eleven-, three-, and two-fold improvement compared to positive control fluorouracil in inhibiting HepG2, PC-3, and A549 cell proliferation with IC₅₀ values of 5.09, 3.70 and 12.74 μM, respectively. Further flow-activated cell sorting analysis revealed that the most promising compound 32 displayed a significant effect on G2/M cell-cycle arrest in a dose-dependent manner in PC-3 cells. These encouraging results should provide important information for the development of new Anticancer agents.

Keywords

1,2,4-Triazolo [3,4-b][1,3,4] thiadiazine; Antiproliferative activity; Furan; Thiophene.

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