Design, Synthesis, in Vitro Cytotoxic Activity Evaluation, and Apoptosis-Induction Study of New 9(10H-Acridinone-1,2,3-Triazoles Publisher Pubmed



Mohammadikhanaposhtani M^{1, 4} ; Safavi M² ; Sabourian R³ ; Mahdavi M^{1, 4} ; Pordeli M⁵ ; Saeedi M⁶ ; Ardestani SK⁵ ; Foroumadi A^{1, 4} ; Shafiee A^{1, 4} ; Akbarzadeh T^{1, 3, 4}
Source: Molecular Diversity Published:2015

Abstract

A new series of 9(10H-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)-1H-1,2,3-triazol-4-yl)methyl)acridin-9(10H-one 8c exhibited the most potency (\hbox {IC}_{50}\,{=}\,11.0\,{\pm }\, 4.8\, \upmu \hbox {M})(IC50=11.0±4.8μM) against MCF-7 cells, being more potent than etoposide (\hbox {IC}_{50}\,{=}\, 12.4\,{\pm }\, 4.7 \upmu \hbox {M})(IC50=12.4±4.7μM). Also, apoptosis induced by compound 8c was confirmed via acridine orange/ethidium bromide and Annexin V-FITC/propidium iodide (PI) double staining. © 2015, Springer International Publishing Switzerland.