2-Alkylsulfanyl estrogen derivatives: synthesis of a novel class of multi-targeted anti-tumour agents.
A flexible, direct, high yielding synthesis of 2-alkylsulfanyl estrogens from estrone has been developed. 2-Methylsulfanyl estradiol (2-MeSE2) 7 displays a similar anti-proliferative activity to the established 2-methoxyestradiol (2-MeOE2) 1, whilst its 3-O-sulfamate derivative (2-MeSE2MATE) 9 exhibits greatly enhanced anti-proliferative activity, combined with significant inhibition of steroid sulfatase, an enzyme target for the treatment of hormone-dependent tumours.
Leese
Mathew P
MP
Medicinal Chemistry, Department of Pharmacy and Pharmacology and Sterix Ltd, University of Bath, Bath BA2 7AY, UK.
Newman
Simon P
SP
Purohit
Atul
A
Reed
Michael J
MJ
Potter
Barry V L
BV
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D004967:Estrogens / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D013463:Sulfuric Acid Esters / Q000008:administration & dosage / Q000737:chemistry
D000970:Antineoplastic Agents; D004967:Estrogens; D013463:Sulfuric Acid Esters