Target-directed enediynes: designed estramycins.
The goal of selective targeting of enediyne cytotoxins has been investigated using estrogenic delivery vehicles. A series of estrogen-enediyne conjugates were assembled, and affinity for human estrogen receptor [hERalpha] was determined. The most promising candidate induced receptor degradation following Bergman cycloaromatization and caused inhibition of estrogen-induced transcription in T47-D human breast cancer cells.
Jones
G B
GB
Department of Chemistry, Northeastern University, Boston, Massachusetts 02115, USA. grjones@lynx.neu.edu
Hynd
G
G
Wright
J M
JM
Purohit
A
A
Plourde
G W
GW
Huber
R S
RS
Mathews
J E
JE
Li
A
A
Kilgore
M W
MW
Bubley
G J
GJ
Yancisin
M
M
Brown
M A
MA
D000480:Alkynes / Q000138:chemical synthesis* / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D003500:Cyclization; D016503:Drug Delivery Systems; D045166:Estradiol Congeners / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000480:Alkynes; D018931:Antineoplastic Agents, Hormonal; D045166:Estradiol Congeners; D011944:Receptors, Androgen; D011960:Receptors, Estrogen