Evaluation of the pharmacophoric motif of the caged Garcinia xanthones.
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.
Chantarasriwong
Oraphin
O
Department of Chemistry & Biochemistry, University of California, San Diego, 9500 Gilman Drive MC: 0358, La Jolla, CA 92093-0358, USA.
Cho
Woo Cheal
WC
Batova
Ayse
A
Chavasiri
Warinthorn
W
Moore
Curtis
C
Rheingold
Arnold L
AL
Theodorakis
Emmanuel A
EA
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*
D000970:Antineoplastic Agents; D044004:Xanthones