Synthesis and biological evaluation of salinomycin triazole analogues as anticancer agents

Salinomycin, a polyether antibiotic used for treatment of coccidial disease in animal husbandry, has demonstrated promising efficacy for treating different cancers. To enrich structure-activity relationship of salinomycin in tumours, we prepared a series of new triazole derivatives in specific site of salinomycin by click cycloaddition reactions, and assessed their antiproliferative activities on breast cancer cell lines. The screening results indicated that most derivatives modified at the C20 hydroxyl group have potent antitumour activity. Notably, salinomycin triazole dimers were 3.27-4.97 times more toxic than the natural substance in ER alpha-positive breast cancer cells (MCF-7), and had moderately improved toxicity in triple-negative breast cancer cells (MDA-MB-231). (C) 2016 Elsevier Masson SAS. All rights reserved.