Design, synthesis, in vitro cytotoxic activity evaluation, and apoptosis-induction study of new 9(10 H)-acridinone-1,2,3-triazoles.

A new series of 9(10 H)-acridinone-1,2,3-triazole derivatives were designed, synthesized and evaluated for their cytotoxic activity against human breast cancer cell lines. The acridone skeleton was prepared through the Ullman condensation of 2-bromobenzoic acid and anilines. Subsequently, it was functionalized with propargyl bromide. Then, a click reaction of the latter compound and in situ prepared 1-(azidomethyl)-4-methoxybenzene derivatives led to the formation of the desired triazole products. Finally, all products were investigated for their capability to cause cytotoxicity against MCF-7, T-47D, and MDA-MB-231 cell lines. Among them, 2-methoxy-10-((1-(4-methoxybenzyl)-1 H-1,2,3-triazol-4-yl)methyl)acridin-9(10 H)-one 8c exhibited the most potency $$(\hbox {IC}_{50}\,{=}\,11.0\,{\pm }\, 4.8\, \upmu \hbox {M})$$ against MCF-7 cells, being more potent than etoposide $$(\hbox {IC}_{50}\,{=}\, 12.4\,{\pm }\, 4.7 \upmu \hbox {M})$$ . Also, apoptosis induced by compound 8c was confirmed via acridine orange/ethidium bromide and Annexin V-FITC/propidium iodide (PI) double staining. [ABSTRACT FROM AUTHOR]