Haploscleridamine, a novel tryptamine-derived alkaloid from a sponge of the order haplosclerida: an inhibitor of cathepsin K.
As part of a search for novel inhibitors of cathepsin K, the MeOH extract of a Micronesian sponge of the order Haplosclerida was shown to be active. Bioassay-guided fractionation of the extract yielded halitoxins, tryptamine, and a novel tryptamine-derived alkaloid, haploscleridamine (1). The tetrahydro-beta-carboline structure of haploscleridamine (1) was elucidated through spectral techniques. Haploscleridamine (1) was found to be an inhibitor of cathepsin K with an IC(50) of 26 microM.
Patil
Ashok D
AD
Department of Drug Discovery, Millennium Pharmaceuticals Inc., 75-5 Sidney Street, Cambridge, Massachusetts 02139-1562, USA.
Freyer
Alan J
AJ
Carte
Brad
B
Taylor
Paul B
PB
Johnson
Randall K
RK
Faulkner
D John
DJ
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D002855:Chromatography, Thin Layer; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D019029:Palau; D011161:Porifera / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D014363:Tryptamines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
D000470:Alkaloids; D015853:Cysteine Proteinase Inhibitors; D014363:Tryptamines; C457258:haploscleridamine; D002403:Cathepsins; D056657:Cathepsin K