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Title

Synthesis and Biological Evaluation of New Podophyllic Aldehyde Derivatives with Cytotoxic and Apoptosis-Inducing Activities

AuthorsIglesia-Vicente, Janis de la; Mollinedo, Faustino
Issue Date2010
PublisherAmerican Chemical Society
CitationJournal of Medicinal Chemistry 53(3): 983-993 (2010)
AbstractSeveral series of nonlactonic podophyllic aldehyde analogues were prepared and evaluated against several human tumor cell lines. They had different combinations of aldehyde, imine, amine, ester, and amide functions at C-9 and C-9′ of the cyclolignan skeleton. All the compounds synthesized showed cytotoxicity levels in the μM range and below. Within the new series tested, compounds having an aldehyde or imine at C-9 and an ester at C-9′ were the most potent, with GI50 values in the nM range, some of them being several times more potent against HT-29 and A-549 carcinoma than against MB-231 melanoma cells. Cell cycle studies and analysis of the microtubule-disrupting capacity have demonstrated the existence of two different mechanisms of cell death induction for compounds with closely related structures. © 2010 American Chemical Society.
URIhttp://hdl.handle.net/10261/63125
DOI10.1021/jm901373w
Identifiersdoi: 10.1021/jm901373w
issn: 0022-2623
e-issn: 1520-4804
Appears in Collections:(IBMCC) Artículos
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