title: Synthesis and biological evaluation of salinomycin triazole analogues as anticancer agents.
abstract: 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 ERα-positive breast cancer cells (MCF-7), and had moderately improved toxicity in triple-negative breast cancer cells (MDA-MB-231).
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, 185 Donghu Road, Wuhan, 430071, China.
authors.forename: Minjian
authors.initials: M
authors.lastname: Huang
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, 185 Donghu Road, Wuhan, 430071, China; Hubei Engineering Laboratory for Synthetic Microbiology, Wuhan Institute of Biotechnology, Wuhan, 430075, China.
authors.forename: Zixin
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, 185 Donghu Road, Wuhan, 430071, China; Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, China. Electronic address: Jian.Tian@whu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Tian
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, 185 Donghu Road, Wuhan, 430071, China; Hubei Engineering Laboratory for Synthetic Microbiology, Wuhan Institute of Biotechnology, Wuhan, 430075, China. Electronic address: liutg@whu.edu.cn.
authors.forename: Tiangang
authors.initials: T
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D061986:MCF-7 Cells; D011714:Pyrans / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D011714:Pyrans; D014230:Triazoles; C010327:salinomycin; D000095662:Polyether Polyketides
keywords: Anticancer activity; Breast cancer; CuAAC reaction; Salinomycin