title: Discovery of novel SERMs with a ferrocenyl entity based on the oxabicyclo[2.2.1]heptene scaffold and evaluation of their antiproliferative effects in breast cancer cells.
abstract: We have synthesized a series of novel SERMs bearing a ferrocenyl unit based on a three-dimensional oxabicyclo[2.2.1]heptene core scaffold. These compounds displayed high receptor binding affinities as well as ERα or ERβ selectivity. In cell proliferation assays, we found that these ligands were cytotoxic at micromolar concentrations in both ER-positive and ER-negative breast cancer cells. On further examination, we found that the antiproliferative effects of compounds 9b, 10h and 11b on MCF-7 cells line does not arise from antiestrogenicity, but rather proceeds through a cytotoxic pathway. Possible mechanisms for the unique activities of these ligands were also investigated by molecular modeling. These new ligands could act as scaffolds for the development of novel anti-breast cancer agents.
authors.affiliation: Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, China.
authors.forename: Yangfan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Caihua
authors.initials: C
authors.lastname: Wang
authors.forename: Changhao
authors.initials: C
authors.lastname: Li
authors.forename: Jinxia
authors.initials: J
authors.lastname: Qiao
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Minjian
authors.initials: M
authors.lastname: Huang
authors.forename: Wenming
authors.initials: W
authors.lastname: Ren
authors.forename: Chune
authors.initials: C
authors.lastname: Dong
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Hai-Bing
authors.initials: HB
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005296:Ferrous Compounds / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000096:biosynthesis; D020845:Selective Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001643:Bridged Bicyclo Compounds; D005296:Ferrous Compounds; D008024:Ligands; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; C116378:bicyclo(2.2.1)heptene; C064804:ferrocenium