A novel type of nonsteroidal estrone sulfatase inhibitors.
Madurahydroxylactone (MHL) is a secondary metabolite produced by the soil bacterium Nonomuria rubra and belongs to the family of benzo[a]naphthacenequinones. We report the initial results and structure-activity relationships of our study into a series of thiosemicarbazone derivatives of madurahydroxylactone as potential nonsteroidal inhibitors of the enzyme estrone sulfatase. The most active compound, the cyclohexylthiosemicarbazone, was shown to be a non-competitive inhibitor with a K(i) of 0.35microM. This compound is devoid of estrogenic properties and showed low acute toxicity in the hen's fertile egg screening test.
Jütten
Peter
P
Hans-Knöll Institute of Natural Products Research, Beutenbergstrasse 1, 07745, Jena, Germany. pjutten@t-online.de
Schumann
Winfried
W
Härtl
Albert
A
Heinisch
Lothar
L
Gräfe
Udo
U
Werner
Walter
W
Ulbricht
Hermann
H
D003596:Cytosine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology; D009279:Naphthacenes / Q000138:chemical synthesis* / Q000494:pharmacology; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology; D011809:Quinones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013429:Sulfatases / Q000037:antagonists & inhibitors*
C465236:6-methoxypurine; D004791:Enzyme Inhibitors; D007783:Lactones; D009279:Naphthacenes; D011687:Purines; D011809:Quinones; C465235:pseudoisocytosine; D003596:Cytosine; D013429:Sulfatases; C020121:estrone sulfatase