Synthesis and antitumoral activity of novel thiazolobenzotriazole, thiazoloindolo[3,2-c]quinoline and quinolinoquinoline derivatives

The biological evaluation of some novel thiazoloindolo[3,2-c]quinoline, 8-substituted-11H-indolo[3,2-c]quinolines is described. These compounds were obtained via Graebe–Ullmann thermal cyclization from appropriated N-arylated benzotriazoles. 7H-4,7-Diaza-benzo[de]anthracene, a reaction by-product structurally closed to the pyridoacridine skeleton was also identified. All thiazolobenzotriazole intermediates were tested in vitro for their capacity to inhibit the growth of two breast cancer cell lines, MCF-7 and MDA-MB-231. In parallel, the newly synthesized skeletons were evaluated for DNA interaction, topoisomerases' inhibition, and cytotoxicity against HL60 and HL60/MX2 human leukemia cells. Most compounds showed a potent growth inhibitory effect on all the tested cell lines, with IC50 in the μM range.

Novel thiazoloindoloquinoline, quinolinoquinoline skeletons prepared from thermal cyclization of benzotriazoles were evaluated for DNA interaction and topoisomerases' inhibition.Figure optionsDownload as PowerPoint slide