Cyclipostins, novel hormone-sensitive lipase inhibitors from Streptomyces sp. DSM 13381. II. Isolation, structure elucidation and biological properties.
Hormone-sensitive lipase (HSL) is a key enzyme of lipid metabolism and its control is therefore a target in the treatment of diabetes mellitus. Cultures of the Streptomyces species DSM 13381 have been shown to potently inhibit HSL. Ten inhibitors of HSL, termed cyclipostins, have been isolated from the mycelium of this microorganism and a further nine related compounds detected. Their structures were characterized by 2-D NMR experiments and by mass spectrometry and were found to comprise neutral cyclic enol phosphate esters with an additional y-lactone ring. On account of their ester-bound fatty alcohol side chain, the cyclipostins have physicochemical properties similar to those of triglycerides. The outstanding characteristic of the cyclipostins is their strong anti-HSL activity, with IC50 values in the nanomolar range.
Aventis Pharma Deutschland GmbH, Drug Innovation & Approval, Frankfurt/Main, Germany. Laszlo.Vertesy@aventis.com
Laszló
L
Vértesy
Bernd
B
Beck
Mark
M
Brönstrup
Klaus
K
Ehrlich
Michael
M
Kurz
Günter
G
Müller
Dietmar
D
Schummer
Gerhard
G
Seibert
D017667:Adipocytes / Q000187:drug effects; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D002787:Sterol Esterase / Q000037:antagonists & inhibitors*; D013302:Streptomyces / Q000254:growth & development / Q000378:metabolism*
D004791:Enzyme Inhibitors; D002787:Sterol Esterase