4,4'-Benzophenone-O,O'-disulfamate: a potent inhibitor of steroid sulfatase.
We investigated whether the benzophenone moiety can be used as core element of steroid sulfatase (STS) inhibitors. While 4- and 3-benzophenone-O-sulfamates inhibit STS with IC(50) values between 5 and 7 microM irrespective of additional hydroxy and methoxy substituents at the second phenyl ring, benzophenone-O,O'-disulfamates show increased activity. With an IC(50) value of 190 nM the 4,4'-derivative is the first small monocyclic STS inhibitor coming close to the potency of the steroidal standard estrone sulfamate.
NOVARTIS Research Institute, Brunnerstrasse 59, A-1235, Vienna, Austria. peter.nussbaumer@pharma.novartis.com
Peter
P
Nussbaumer
Melitta
M
Bilban
Andreas
A
Billich
D001192:Arylsulfatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001577:Benzophenones / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D043266:Steryl-Sulfatase; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000737:chemistry / Q000494:pharmacology
C473954:4,4'-Benzophenone-O,O'-disulfamate; D001577:Benzophenones; D013451:Sulfonic Acids; D001192:Arylsulfatases; D043266:Steryl-Sulfatase