Synthesis and structure-activity relationships of 2- and/or 4-halogenated 13ß- and 13α-estrone derivatives as enzyme inhibitors of estrogen biosynthesis.
J Enzyme Inhib Med Chem
; 33(1): 1271-1282, 2018 Dec.
Article
in En
| MEDLINE
| ID: mdl-30230387
ABSTRACT
Ring A halogenated 13α-, 13ß-, and 17-deoxy-13α-estrone derivatives were synthesised with N-halosuccinimides as electrophile triggers. Substitutions occurred at positions C-2 and/or C-4. The potential inhibitory action of the halogenated estrones on human aromatase, steroid sulfatase, or 17ß-hydroxysteroid dehydrogenase 1 activity was investigated via in vitro radiosubstrate incubation. Potent submicromolar or low micromolar inhibitors were identified with occasional dual or multiple inhibitory properties. Valuable structure-activity relationships were established from the comparison of the inhibitory data obtained. Kinetic experiments performed with selected compounds revealed competitive reversible inhibition mechanisms against 17ß-hydroxysteroid dehydrogenase 1 and competitive irreversible manner in the inhibition of the steroid sulfatase enzyme.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aromatase
/
Steryl-Sulfatase
/
Enzyme Inhibitors
/
Estradiol Dehydrogenases
/
Estrogens
/
Estrone
Limits:
Humans
Language:
En
Journal:
J Enzyme Inhib Med Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2018
Document type:
Article
Affiliation country:
Hungary