Rapid evaluation of Antrodia camphorata natural products and derivatives in tumourigenic liver progenitor cells with a novel cell proliferation assay.
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.
Stewart
Scott G
SG
The School of Biomedical, Biomolecular & Chemical Sciences, The University of Western Australia, Crawley, Crawley, WA 6009 (Australia). sgs@cyllene.uwa.edu.au
Ho
Louisa A
LA
Polomska
Marta E
ME
Percival
Alexander T
AT
Yeoh
George C T
GC
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
D000970:Antineoplastic Agents; D001688:Biological Products; D008299:Maleic Anhydrides; D008301:Maleimides