Synthesis and anticancer activity of [1,2,4] triazole [4,3-b] [1,2,4,5] tetrazine derivatives

Abstract

A series of [1,2,4] triazole [4,3-b] [1,2,4,5] tetrazine derivatives were synthesized, and they were screened for their anticancer activity against human lung cancer (A549), mouse normal hepatocytes (AML12), human colorectal adenocarcinoma (CaCo2), human gastric cancer (EGC), human hepatocellular carcinoma (HEPG2) and human colon carcinoma (HT-29) cell lines. Among them, compound 4g (8-((6-(3,5-Dimethyl-1H-pyrazol-1-yl)-[1,2,4] triazolo[4,3-b][1,2,4,5]tetrazin-3-ylthio)methyl)quinoline) performed well, and its IC₅₀ value against human colon carcinoma (HT-29) cell was 12.69 ± 7.14 µM.

Graphical Abstract

Keywords:

• Triazole
• tetrazine
• synthesis
• antitumor activity

Acknowledgments

The authors are very grateful to the Medicinal Chemistry Innovation Team of Taizhou Vocational & Technical College, the Zhejiang Public Welfare Technology Research Project (LGF19B020001), the Taizhou Science and Technology Project (1902GY27), Research and Cultivation Project of Taizhou Vocational and Technical College–Synthesis and Bioactivity Evaluation of new tetrazine antitumor drugs (2021PY05) and the Key Research and Development Program of Changzhou (Social Development, No. CE20205058).

Additional information

Funding

The authors are very grateful to the Medicinal Chemistry Innovation Team of Taizhou Vocational & Technical College, the Zhejiang Public Welfare Technology Research Project (LGF19B020001), the Taizhou Science and Technology Project (1902GY27), Research and Cultivation Project of Taizhou Vocational and Technical College–Synthesis and Bioactivity Evaluation of new tetrazine antitumor drugs (2021PY05) and the Key Research and Development Program of Changzhou (Social Development, No. CE20205058).