Synthesis of 17beta-estradiol-platinum(II) hybrid molecules showing cytotoxic activity on breast cancer cell lines.
The synthesis of a series of 17beta-estradiol-platinum(II) hybrid molecules is reported. The hybrids are made of a PEG linking chain of various length and a 2-(2'-aminoethyl)pyridine ligand. They are prepared from estrone in five chemical steps with an overall yield of 22%. The length of the PEG chain does not influence the solubility of the compounds as it remains relatively constant throughout the series. MTT assays showed that the derivative with the longest PEG chain showed the best activity against breast cancer cell lines (MCF-7 and MDA-MB-231). Molecular modeling study rationalized the results.
Provencher-Mandeville
Josée
J
Département de Chimie-Biologie, Groupe de Recherche en Biopathologies Cellulaires et Moléculaires, Université du Québec à Trois-Rivières, C.P. 500, Trois-Rivières, Que., Canada G9A 5H7.
Descôteaux
Caroline
C
Mandal
Sanat K
SK
Leblanc
Valérie
V
Asselin
Eric
E
Bérubé
Gervais
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D005260:Female; D006801:Humans; D008024:Ligands; D008956:Models, Chemical; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry; D013329:Structure-Activity Relationship
C487473:17beta-estradiol platinum(II); D000970:Antineoplastic Agents; D008024:Ligands; D009944:Organoplatinum Compounds; D011725:Pyridines; D004958:Estradiol