title: Synthesis, biological evaluation and structure-activity relationship studies of isoflavene based Mannich bases with potent anti-cancer activity.
abstract: Phenoxodiol, an analogue of the isoflavone natural product daidzein, is a potent anti-cancer agent that has been investigated for the treatment of hormone dependent cancers. This molecular scaffold was reacted with different primary amines and secondary amines under different Mannich conditions to yield either benzoxazine or aminomethyl substituted analogues. These processes enabled the generation of a diverse range of analogues that were required for structure-activity relationship (SAR) studies. The resulting Mannich bases exhibited prominent anti-proliferative effects against SHEP neuroblastoma and MDA-MB-231 breast adenocarcinoma cell lines. Further cytotoxicity studies against MRC-5 normal lung fibroblast cells showed that the isoflavene analogues were selective towards cancer cells.
authors.affiliation: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia; Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Shelley L
authors.initials: SL
authors.lastname: Cass
authors.affiliation: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Kutty
authors.affiliation: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia; Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia.
authors.forename: Eugene M H
authors.initials: EM
authors.lastname: Yee
authors.affiliation: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Daniel S H
authors.initials: DS
authors.lastname: Chan
authors.affiliation: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia; Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Gardner
authors.affiliation: Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; Australian Centre for NanoMedicine, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Orazio
authors.initials: O
authors.lastname: Vittorio
authors.affiliation: Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; Metronomics Global Health Initiative, Marseille, France.
authors.forename: Eddy
authors.initials: E
authors.lastname: Pasquier
authors.affiliation: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: David StC
authors.initials: DS
authors.lastname: Black
authors.affiliation: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia; Australian Centre for NanoMedicine, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: n.kumar@unsw.edu.au.
authors.forename: Naresh
authors.initials: N
authors.lastname: Kumar
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007529:Isoflavones / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D008352:Mannich Bases / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007529:Isoflavones; D008352:Mannich Bases; C065753:isoflavanone
keywords: Anti-cancer; Benzoxazine; Isoflavene; Mannich base; Phenoxodiol