title: Haploscleridamine, a novel tryptamine-derived alkaloid from a sponge of the order haplosclerida: an inhibitor of cathepsin K.
abstract: 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.
authors.affiliation: Department of Drug Discovery, Millennium Pharmaceuticals Inc., 75-5 Sidney Street, Cambridge, Massachusetts 02139-1562, USA.
authors.forename: Ashok D
authors.initials: AD
authors.lastname: Patil
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Freyer
authors.forename: Brad
authors.initials: B
authors.lastname: Carte
authors.forename: Paul B
authors.initials: PB
authors.lastname: Taylor
authors.forename: Randall K
authors.initials: RK
authors.lastname: Johnson
authors.forename: D John
authors.initials: DJ
authors.lastname: Faulkner
mesh_terms: 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
chemical_list: D000470:Alkaloids; D015853:Cysteine Proteinase Inhibitors; D014363:Tryptamines; C457258:haploscleridamine; D002403:Cathepsins; D056657:Cathepsin K