title: Rapid evaluation of Antrodia camphorata natural products and derivatives in tumourigenic liver progenitor cells with a novel cell proliferation assay.
abstract: We report the syntheses of five natural product maleimide and maleic anhydrides from the mushroom Antrodia camphorata. The ability of these compounds to affect proliferation in non-tumourigenic and tumourigenic liver progenitor cell lines was monitored by the Cellscreen system, a novel and nondestructive rapid-screening instrument. Additionally, a range of new aryl-functionalised differentiated derivatives were prepared through a Suzuki cross-coupling reaction to influence cell-growth effects. Several derivatives radically slowed the proliferation of liver progenitor cells; however, of particular interest were two maleic anhydride derivatives containing aryl tethers. These analogues demonstrated selectivity for limiting the proliferation of tumourigenic progenitor cells in comparison with their non-tumourigenic counterparts. Also highlighted is the application of the Cellscreen system in medicinal chemistry to rapidly measure the effect of compound libraries on cell proliferation.
authors.affiliation: The School of Biomedical, Biomolecular & Chemical Sciences, The University of Western Australia, Crawley, Crawley, WA 6009 (Australia). sgs@cyllene.uwa.edu.au
authors.forename: Scott G
authors.initials: SG
authors.lastname: Stewart
authors.forename: Louisa A
authors.initials: LA
authors.lastname: Ho
authors.forename: Marta E
authors.initials: ME
authors.lastname: Polomska
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Percival
authors.forename: George C T
authors.initials: GC
authors.lastname: Yeoh
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D055491:Antrodia / Q000737:chemistry*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008299:Maleic Anhydrides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008301:Maleimides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology; D014410:Tumor Stem Cell Assay
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D008299:Maleic Anhydrides; D008301:Maleimides