Synthesis and antiproliferative activity of novel steroidal dendrimer conjugates.
We describe the synthesis of steroidal dendrimer conjugates of first and second generation with tetramethylene core and 5-hydroxy-isophtalic acid dimethyl ester as branching unit modified to incorporate ethynylestradiol or 17α-estradiol as terminal units. The steroidal dendrimer conjugates, the free drug (steroids) and dendrimer were tested against a panel of cancer cell lines (CEM, MCF7, HeLa) and normal human fibroblast (BJ). The steroidal dendrimer conjugates of first generation exhibited cytotoxic activity and induced apoptosis in chronic leukemia (CEM) as resultant activation of caspase cascade which is mainly provoked in G2/M arrested cells.
Departamento de Química, Centro de Investigación y de Estudios Avanzados del IPN, Apdo. Postal 14-740, México D.F. 07000, Mexico.
Nancy E
NE
Magaña-Vergara
Lucie
L
Rárová
Delia
D
Soto-Castro
Norberto
N
Farfán
Miroslav
M
Strnad
Rosa
R
Santillan
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D050091:Dendrimers / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D008958:Models, Molecular; D008968:Molecular Conformation
D000970:Antineoplastic Agents; D050091:Dendrimers; D004958:Estradiol; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7
Antiproliferative activity; Ethynylestradiol; Steroidal dendrimer conjugates