Design and synthesis of novel 1,2,3,4-tetrazines as new anti-leukemia cancer agents

Eyilcim O., Gunay F., GÜNKARA Ö. T., Ng Y. Y., Ulucan O., Erden I.

Chemical Biology and Drug Design, vol.102, no.5, pp.1186-1201, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 102 Issue: 5
  • Publication Date: 2023
  • Doi Number: 10.1111/cbdd.14328
  • Journal Name: Chemical Biology and Drug Design
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.1186-1201
  • Keywords: 1,2,3,4-tetrazine renal fibrosis, anticancer activity, azaoxyallyl cations, leukemia cell line, MTT assay
  • Yıldız Technical University Affiliated: Yes

Abstract

A series of novel 1,2,3,4-tetrazines were designed and synthesized. 1H-NMR spectroscopy, 13C NMR spectroscopy, and HRMS were used to determine the structures of this novel compounds. Computational approaches suggested that DHFR is a putative target for the newly synthesized 11 compounds. Extensive molecular dynamics simulations followed by molecular docking simulations were employed to evaluate DHFR as a potential target protein. The anticancer activities of the compounds were evaluated against five different types of leukemia cell lines (Jurkat, Nalm-6, Reh, K562, and Molt-4) and one non-leukemic cell line (Hek293T) by MTT test in vitro and imatinib was used as a control drug. Among these compounds, 3a exhibited the best activity against all the leukemic cell lines, except Reh cell line. For Nalm-6, K562, Jurkat, and Molt-4 cell lines, IC50 values were found to be 15.98, 19.12, 23.15, and 25.80 μM, respectively. Our work focuses on the synthesis of original and novel 1,2,3,4-tetrazine derivatives while contributing to the ongoing effort to discover more potent new antileukemia agents.