Journal of Enzyme Inhibition and Medicinal Chemistry (Jan 2021)

Design, synthesis and biological evaluation of 1-Aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as novel microtubule destabilizers

  • Chao Wang,
  • Yuelin Li,
  • Zi Liu,
  • Zeyu Wang,
  • Zihan Liu,
  • Shuai Man,
  • Yujing Zhang,
  • Kai Bao,
  • Yingliang Wu,
  • Qi Guan,
  • Daiying Zuo,
  • Weige Zhang

DOI
https://doi.org/10.1080/14756366.2020.1759582
Journal volume & issue
Vol. 36, no. 1
pp. 549 – 560

Abstract

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A series of 1-aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as microtubule destabilizers were designed, synthesised and evaluated for anticancer activity. Based on bioisosterism, we introduced the tetrazole moiety containing the hydrogen-bond acceptors as B-ring of XRP44X analogues. The key intermediates ethyl 1-aryl-1H-tetrazole-5-carboxylates 10 can be simply and efficiently prepared via a microwave-assisted continuous operation process. Among the compounds synthesised, compound 6–31 showed noteworthy potency against SGC-7901, A549 and HeLa cell lines. In mechanism studies, compound 6–31 inhibited tubulin polymerisation and disorganised microtubule in SGC-7901 cells by binding to tubulin. Moreover, compound 6–31 arrested SGC-7901cells in G2/M phase. This study provided a new perspective for development of antitumor agents that target tubulin.

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