Ergosteroids V: preparation and biological activity of various D-ring derivatives in the 7-oxo-dehydroepiandrosterone series.
Our previous finding that D-ring seco derivatives of dehydroepiandrosterone retained biologic activity (Reich et al., Steroids 1998;63:542-53) motivated us to synthesize and test a number of steroids in which the D-ring is retained but altered in various ways. Several new steroids were synthesized and characterized by (1)H and (13)C NMR spectroscopy. The availability of a number of closely related compounds allowed detailed (13)C chemical shift correlations. Using the induction of two thermogenic enzymes in rats, liver mitochondrial glycerophosphate dehydrogenase (GPDH) and cytosolic malic enzyme, as criteria of biologic activity some 30 compounds were assayed. Hydroxylation of dehydroepiandrosterone (DHEA) at the 16 alpha position was previously shown to diminish activity (Lardy et al., Steroids 1998;63:158-65); the corresponding 7-oxo compound is fully active. Hydroxylation at the 15 beta position of DHEA, 7-oxo-DHEA, or 16 alpha-hydroxy-7-oxo-DHEA greatly diminished the induction of GPDH but induction of malic enzyme was retained. Most 5,15 diene steroids tested had 2 weak, or no, ability to enhance the formation of GPDH but did increase malic enzyme.
Reich
Ieva L
IL
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA.
Reich
Hans J
HJ
Kneer
Nancy
N
Lardy
Henry
H
D000738:Androsterone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D003687:Dehydroepiandrosterone / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005993:Glycerolphosphate Dehydrogenase / Q000096:biosynthesis; D006900:Hydroxylation; D008099:Liver / Q000648:ultrastructure; D009682:Magnetic Resonance Spectroscopy; D008291:Malate Dehydrogenase / Q000096:biosynthesis; D008930:Mitochondria, Liver / Q000201:enzymology; D051381:Rats; D013329:Structure-Activity Relationship
D003687:Dehydroepiandrosterone; D000738:Androsterone; D005993:Glycerolphosphate Dehydrogenase; D008291:Malate Dehydrogenase