Design, synthesis, in vitro cytotoxic activity evaluation, and apoptosis-induction study of new 9(10H)-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 ( IC 50 = 11.0 ± 4.8 μ M ) against MCF-7 cells, being more potent than etoposide ( IC 50 = 12.4 ± 4.7 μ M ) . Also, apoptosis induced by compound 8c was confirmed via acridine orange/ethidium bromide and Annexin V-FITC/propidium iodide (PI) double staining.