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Publication
Insights into the in vitro antitumor mechanism of action of a new pyranoxanthone
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Advisor(s)
Abstract(s)
Naturally occurring xanthones have been docu mented as having antitumor properties, with some
of them presently undergoing clinical trials. In an
attempt to improve the biological activities of
dihydroxyxanthones, prenylation and other mole cular modifications were performed. All the com pounds reduced viable cell number in a leukemia
cell line K-562, with the fused xanthone 3,
4-dihydro-12-hydroxy-2,2-dimethyl-2H,6H-pyrano[3,
2-b]xanthen-6-one (5) being the most potent. The
pyranoxanthone 5 was particularly effective in
additional leukemia cell lines (HL-60 and BV-173).
Furthermore, the pyranoxanthone 5 decreased cel lular proliferation and induced an S-phase cell
cycle arrest. In vitro, the pyranoxanthone 5
increased the percentage of apoptotic cells which
was confirmed by an appropriate response at the
protein level (e.g., PARP cleavage). Using a com puter screening strategy based on the structure of
several anti- and pro-apoptotic proteins, it was
verified that the pyranoxanthone 5 may block the
binding of anti-apoptotic Bcl-xL to pro-apoptotic
Bad and Bim. The structure-based screening
revealed the pyranoxanthone 5 as a new scaffold
that may guide the design of small molecules with
better affinity profile for Bcl-xL.
Description
Keywords
Antiproliferation Apoptosis Bcl-xL Leukemia Structure-based screening Xanthone . Faculdade de Ciências Exatas e da Engenharia
Citation
Palmeira, A., Paiva, A., Sousa, E., Seca, H., Almeida, G. M., Lima, R. T., ... & Vasconcelos, M. H. (2010). Insights into the in vitro antitumor mechanism of action of a new pyranoxanthone. Chemical biology & drug design, 76(1), 43-58.
Publisher
Wiley