Discovery of Novel Tricyclic 5H-Pyridazino[4,5-b]indoles as Potent Antitumor Agents: Design,Synthesis and Biological Evaluation

A novel series of 5H-pyridazino4,5-b]indoles(L-01-L-32) was synthesized and characterized by means of ¹H NMR, MS and elemental analysis. The cytotoxicity of the target compounds against Bel-7402 and HT-1080 cell lines were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. Most of them exhibited moderate to excellent cytotoxicity, and six compounds(L-04, L-06, L-18, L-20, L-21 and L-23) possessed dramatically increased cytotoxicity superior to Gefitinib. Of these initial hits, compound L-21 displayed remarkable cytotoxicity against the tested cell lines with half maximal inhibitory concentration(IC₅₀) values of 4.6 and 2.1 μmol/L, respectively, which was 13.9- to 25.6-fold more potent than positive control.