Synthesis and cytotoxicity of hydrophobic esters of podophyllotoxins.
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.
López-Pérez
J L
JL
Departamento de Química Farmacéutica, Universidad de Salamanca, 37007 Salamanca, Spain. lopez@usal.es
del Olmo
E
E
de Pascual-Teresa
B
B
Abad
A
A
San Feliciano
A
A
D000818:Animals; D045744:Cell Line, Tumor; D004952:Esters; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008811:Mice, Inbred DBA; D011034:Podophyllotoxin / Q000138:chemical synthesis* / Q000633:toxicity*
D004952:Esters; D011034:Podophyllotoxin