title: Evaluation of the pharmacophoric motif of the caged Garcinia xanthones.
abstract: The combination of unique structure and potent bioactivity exhibited by several family members of the caged Garcinia xanthones, led us to evaluate their pharmacophore. We have developed a Pd(0)-catalyzed method for the reverse prenylation of catechols that, together with a Claisen/Diels-Alder reaction cascade, provides rapid and efficient access to various caged analogues. Evaluation of the growth inhibitory activity of these compounds leads to the conclusion that the intact ABC ring system containing the C-ring caged structure is essential to the bioactivity. Studies with cluvenone (7) also showed that these compounds induce apoptosis and exhibit significant cytotoxicity in multidrug-resistant leukemia cells. As such, the caged Garcinia xanthone motif represents a new and potent pharmacophore.
authors.affiliation: Department of Chemistry & Biochemistry, University of California, San Diego, 9500 Gilman Drive MC: 0358, La Jolla, CA 92093-0358, USA.
authors.forename: Oraphin
authors.initials: O
authors.lastname: Chantarasriwong
authors.forename: Woo Cheal
authors.initials: WC
authors.lastname: Cho
authors.forename: Ayse
authors.initials: A
authors.lastname: Batova
authors.forename: Warinthorn
authors.initials: W
authors.lastname: Chavasiri
authors.forename: Curtis
authors.initials: C
authors.lastname: Moore
authors.forename: Arnold L
authors.initials: AL
authors.lastname: Rheingold
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Theodorakis
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004341:Drug Evaluation; D004354:Drug Screening Assays, Antitumor; D029760:Garcinia / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D044004:Xanthones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D044004:Xanthones