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

Abstract

AbstractA 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.