N1-0066 — Interim report
1.
Synthesis and structure-activity relationships of 2- and/or 4-halogenated 13[beta]- and 13[alpha]-estrone derivatives as enzyme inhibitors of estrogen biosynthesis

Ring A halogenated 13[alpha], 13[beta], and 17-deoxy-13[alpha]-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 17[beta]-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 17[beta]-hydroxysteroid dehydrogenase 1 and competitive irreversible manner in the inhibition of the steroid sulfatase enzyme.

COBISS.SI-ID: 33949401