title: Development of constrained tamoxifen mimics and their antiproliferative properties against breast cancer cells.
abstract: An efficient synthesis of a new series of tamoxifen mimics is described by employing iodine catalyzed ipsocyclization strategy followed by Suzuki coupling. A molecular docking studies of the synthesized compounds 11a-n and 12 in estrogen receptor (ER-α) showed that the scaffolds are fitting well in the groove, thereby suggesting them as promising antiproliferative agents for estrogen dependent breast cancer lines. All compounds were tested in vitro against breast cancer cell lines-ER positive, MCF-7; ER negative, MDA-MB-231; and control mammary epithelial cells, MEpiC. The biological results showed that most of the compounds are active against MCF-7 with IC50 values less than 6.5μM which corroborate the results of molecular docking studies.
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Archana
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; Academy for Scientific Innovation and Research, New Delhi 110001, India.
authors.forename: Ramasatyaveni
authors.initials: R
authors.lastname: Geesala
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Narasimha B
authors.initials: NB
authors.lastname: Rao
authors.affiliation: Institute of Life Sciences, Bhubaneswar 751023, India.
authors.forename: Suresh
authors.initials: S
authors.lastname: Satpati
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Giridhar
authors.initials: G
authors.lastname: Puroshottam
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Akhila
authors.initials: A
authors.lastname: Panasa
authors.affiliation: Institute of Life Sciences, Bhubaneswar 751023, India.
authors.forename: Anshuman
authors.initials: A
authors.lastname: Dixit
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; Academy for Scientific Innovation and Research, New Delhi 110001, India.
authors.forename: Amitava
authors.initials: A
authors.lastname: Das
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; Academy for Scientific Innovation and Research, New Delhi 110001, India. Electronic address: aksrivastava@iict.res.in.
authors.forename: Ajay Kumar
authors.initials: AK
authors.lastname: Srivastava
mesh_terms: D001665:Binding Sites; D001897:Boronic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D010165:Palladium / Q000737:chemistry; D017434:Protein Structure, Tertiary; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity
chemical_list: D001897:Boronic Acids; D056831:Coordination Complexes; D047628:Estrogen Receptor alpha; D013629:Tamoxifen; D010165:Palladium
keywords: Breast cancer; Ipsocyclization; Molecular docking; SERMs; Tamoxifen