title: Discovery of Tröger's base analogues as selective inhibitors against human breast cancer cell line: design, synthesis and cytotoxic evaluation.
abstract: A library of structurally diverse Tröger's base analogues has been constructed via unusual amination of methylene bridge employing Vilsmeier-Haack conditions as well as by the incorporation of five and six membered heterocycles on the aromatic core of Tröger's base framework. The constructed structurally diverse frameworks were evaluated for their cytotoxic activities against a panel of three human cancer lines A549 (lung adenocarcinoma), MDAMB-231 (breast) and SK-N-SH (neuroblastoma). From the activity profile obtained, a redesign of Tröger's base analogues led to the construction of more potent molecular entities. The study led to development of a series of compounds with MDAMB-231 cell line specific cytotoxicity. Of the 30 compounds synthesized and evaluated, 7 compounds were found to possess cytotoxicity that is equivalent or better than standard drug doxorubicin against MDAMB-231 cell line while only one compound was found to be active against SK-N-SH cell line.
authors.affiliation: Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 607, India.
authors.forename: Bhaskar Reddy
authors.initials: BR
authors.lastname: Manda
authors.affiliation: Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 607, India. Electronic address: manjula@iict.res.in.
authors.forename: Manjula
authors.initials: M
authors.lastname: Alla
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 607, India.
authors.forename: Roopa Jones
authors.initials: RJ
authors.lastname: Ganji
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 607, India. Electronic address: anthony@iict.res.in.
authors.forename: Anthony
authors.initials: A
authors.lastname: Addlagatta
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001392:Azocines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001392:Azocines; C083830:Troeger's base
keywords: Amination; Cytotoxicity; Tröger's base; Vilsmeier–Haack reaction