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ID: ALA1147606

Journal: Bioorg Med Chem Lett

Title: Synthesis and cytotoxicity of hydrophobic esters of podophyllotoxins.

Authors: López-Pérez JL, del Olmo E, de Pascual-Teresa B, Abad A, San Feliciano A.

Abstract: Diverse norbornenecarboxylate esters of podophyllotoxin and its epimers and diastereoisomers have been prepared through Diels-Alder cycloaddition by treating the dienophilic acrylates of cyclolignans with cyclopentadiene. Their cytotoxicities against several cancer cell lines have been evaluated and the results compared with those found for other lignan esters. Podophyllotoxin adducts showed a one-fold increase in activity when compared to the natural product. The preparation of more hydrophobic esters, which showed less cytotoxicity, demonstrated that this activity is not primarily due to the lipophilic factor, but mainly to the spatial arrangement of the bulky moiety, which could contribute to increase the binding to the target site.

CiteXplore: 14980682

DOI: 10.1016/j.bmcl.2003.12.039