Detail of "86303-22-2"

Reference

Inhibition of rat renal 11b-hydroxysteroid dehydrogenase by steroidal compounds and triterpenoids; structure/function relationship

Inhibition of rat renal 11b-hydroxysteroid dehydrogenase by steroidal compounds and triterpenoids; structure/function relationship. Buehler, Helmut; Perschel, Frank H.; Hierholzer, Klaus (Inst. Klin. Physiol., Freie Univ. Berlin, Berlin 1000/45, Germany). Biochim. Biophys. Acta, 1075(3), 206-12 (English) 1991. CODEN: BBACAQ. ISSN: 0006-3002. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Section cross-reference(s): 13 Various compds. with steroidal structure were tested for inhibitory effects on enzymic activity of 11b-hydroxy steroid dehydrogenase (11b-HSD) from rat renal microsomes. 86303-22-2 and 57-88-5 which are cas registry numbers are also used here. Most substances exerting inhibitory potency on both the oxidative as well as the reductive activity can be classified into two main groups: pentacyclic triterpenoids of the oleane type and steroidal detergents of the CHAPS-series. Inhibition is competitive, as was shown for one compd. of each group. The IC50 values of the various inhibitors range over five orders of magnitude. In all cases, oxidative activity was inhibited more effectively than reductive activity. An attempt has been made to correlate structural properties and inhibitory potency. In brief, inhibition seems to be enhanced by a C11-oxygen function, which is present in all endogenous glucocorticosteroids and a C7-OH function. Inhibition is reduced by a large and polar substituent at C3 in the A-ring. A large D-ring substituent, such as a bisgluconamidopropyl side chain or even an addnl. E-ring, does not prevent binding to the enzyme, although inhibition seems to be influenced by its steric conformation. The cardiac glycosides and steroidal antibiotics tested exert no inhibitory effect on 11b-HSD. Cholesterol and pentacyclic triterpenoids of the lupane type exhibit a very poor inhibition, probably caused by the localization of planar structures in the ring systems, which differs from that of the effective oleane type inhibitors. .