title: Synthesis and structure-activity relationships of novel hybrid ferrocenyl compounds based on a bicyclic core skeleton for breast cancer therapy.
abstract: Breast cancer is the most frequent cancer in women worldwide, and incidence is increasing year by year. Although current selective estrogen receptor modulators (SERMs) have clear advantages in the treatment of hormone-responsive breast cancer, they are ineffective for ER(-). In this study, we describe the design and synthesis of a series of dual-acting estrogen receptor (ER) and histone deacetylase (HDAC) inhibitors with incorporation of the ferrocenyl moiety, leading to novel hybrid ferrocenyl complexes (FcOBHS-HDACis) for breast cancer therapy. It is worth to note that these ferrocenyl conjugates could not only potently inhibit HDACs and the proliferation of ERα positive (ER(+)) breast cancer cells (MCF-7), but also show significant antiproliferative effect on ER(-) breast cancer cells (MDA-MB-231). Thus, the FcOBHS-HDACi conjugates represent a novel approach to the development of efficiently dual-acting agents for treatment of breast cancer.
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Changhao
authors.initials: C
authors.lastname: Li
authors.affiliation: Hubei Provincial Key Laboratory of Developmentally Originated Disease, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors.forename: Chu
authors.initials: C
authors.lastname: Tang
authors.affiliation: Hubei Provincial Key Laboratory of Developmentally Originated Disease, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors.forename: Zhiye
authors.initials: Z
authors.lastname: Hu
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Hubei Provincial Key Laboratory of Developmentally Originated Disease, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors.forename: Chenlu
authors.initials: C
authors.lastname: Li
authors.affiliation: Hubei Provincial Key Laboratory of Developmentally Originated Disease, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors.forename: Silong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Hubei Provincial Key Laboratory of Developmentally Originated Disease, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors.forename: Chune
authors.initials: C
authors.lastname: Dong
authors.affiliation: Hubei Provincial Key Laboratory of Developmentally Originated Disease, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China. Electronic address: zhouhb@whu.edu.cn.
authors.forename: Hai-Bing
authors.initials: HB
authors.lastname: Zhou
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: jianhuang@whu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
mesh_terms: D001665:Binding Sites; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005296:Ferrous Compounds / Q000737:chemistry* / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008954:Models, Biological; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D011960:Receptors, Estrogen / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001643:Bridged Bicyclo Compounds; D005296:Ferrous Compounds; D056572:Histone Deacetylase Inhibitors; D011960:Receptors, Estrogen; D006655:Histone Deacetylases
keywords: Breast cancer; Ferrocenyl; HDACi; SERMs