2. Academic Validation
  3. Novel [1,2,3]triazolo[4,5-d]pyrimidine derivatives containing hydrazone fragment as potent and selective anticancer agents

Novel [1,2,3]triazolo[4,5-d]pyrimidine derivatives containing hydrazone fragment as potent and selective anticancer agents

  • Bioorg Chem. 2020 Dec;105:104424. doi: 10.1016/j.bioorg.2020.104424.
Chenhao Xu 1,  Wenjuan Zhou 2,  Guanjun Dong 1,  Hui Qiao 1,  Jiadi Peng 1,  Pengfei Jia 1,  Yuhao Li 1,  Hongmin Liu 1,  Kai Sun 3,  Wen Zhao 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Zhengzhou University School of Pharmaceutical Sciences and Institute of Drug Discovery & Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.
  • 2 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Zhengzhou University School of Pharmaceutical Sciences and Institute of Drug Discovery & Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China; Department of Pathology, Oslo University Hospital, Faculty of Medicine, University of Oslo, Oslo 0379, Norway.
  • 3 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Zhengzhou University School of Pharmaceutical Sciences and Institute of Drug Discovery & Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China. Electronic address: [email protected].
  • 4 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Zhengzhou University School of Pharmaceutical Sciences and Institute of Drug Discovery & Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China. Electronic address: [email protected].
PMID: 33161253 DOI: 10.1016/j.bioorg.2020.104424
Abstract

In this paper, based on molecular hybridization, a series of [1,2,3]triazolo[4,5-d]pyrimidine derivatives containing hydrazine was synthesized and their antiproliferative activities against 5 Cancer cell lines (MGC-803, PC3, PC9, EC9706 and SMMC-7721) were evaluated. We found that most of them exhibited obvious growth inhibition effects on these tested Cancer cells, especially compound 34 on PC3 cells (IC50 = 26.25 ± 0.28 nM). Meanwhile, compound 34 displayed best selectivity on PC3, compared with the other Cancer cell lines, as well as excellent selectivity towards normal cell lines (Het-1A, L02 and GES-1). Further investigations demonstrated that 34 could significantly inhibit PC3 cells' colony formation, increase cellular ROS content, suppress EGFR expression and induce Apoptosis. Our findings indicate that 34 may serve as a novel lead compound for the discovery of more triazolopyrimidine derivatives with improved Anticancer potency and selectivity.

Keywords

Anti-prostatic; Apoptosis; EGFR; Hydrazone; ROS; [1,2,3]triazolo[4,5-d]pyrimidine.

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