title: Synthesis and Biological Evaluation of Kibdelone C and Its Simplified Derivatives.
abstract: Poylcyclic tetrahydroxanthones comprise a large class of cytototoxic natural products. No mechanism of action has been described for any member of the family. We report the synthesis of kibdelone C and several simplified analogs. Both enantiomers of kibdeleone C show low nanomolar cytotoxicity toward multiple human cancer cell lines. Moreover, several simplified derivatives with improved chemical stability display higher activity than the natural product itself. In vitro studies rule out interaction with DNA or inhibition of topoisomerase, both of which are common modes of action for polycyclic aromatic compounds. However, celluar studies reveal that kibdelone C and its simplified derivatives disrupt the actin cytoseketon without directly binding actin or affecting its polymerization in vitro.
authors.affiliation: Department of Biochemistry and ‡Department of Internal Medicine, UT Southwestern Medical Center , 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
authors.forename: Janjira
authors.initials: J
authors.lastname: Rujirawanich
authors.affiliation: Department of Biochemistry and ‡Department of Internal Medicine, UT Southwestern Medical Center , 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and ‡Department of Internal Medicine, UT Southwestern Medical Center , 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
authors.forename: Ai-Jun
authors.initials: AJ
authors.lastname: Ma
authors.affiliation: Department of Biochemistry and ‡Department of Internal Medicine, UT Southwestern Medical Center , 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
authors.forename: John R
authors.initials: JR
authors.lastname: Butler
authors.affiliation: Department of Biochemistry and ‡Department of Internal Medicine, UT Southwestern Medical Center , 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
authors.forename: Yizhong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and ‡Department of Internal Medicine, UT Southwestern Medical Center , 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and ‡Department of Internal Medicine, UT Southwestern Medical Center , 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Rosen
authors.affiliation: Department of Biochemistry and ‡Department of Internal Medicine, UT Southwestern Medical Center , 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
authors.forename: Bruce
authors.initials: B
authors.lastname: Posner
authors.affiliation: Department of Biochemistry and ‡Department of Internal Medicine, UT Southwestern Medical Center , 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
authors.forename: Deepak
authors.initials: D
authors.lastname: Nijhawan
authors.affiliation: Department of Biochemistry and ‡Department of Internal Medicine, UT Southwestern Medical Center , 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Ready
mesh_terms: D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D044004:Xanthones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D044004:Xanthones; C574351:kibdelone C