Haploscleridamine, a Novel Tryptamine-Derived Alkaloid from a Sponge of the Order Haplosclerida:  An Inhibitor of Cathepsin K

• Published in: Journal of natural products (Washington, D.C.) Vol. 65; no. 4; pp. 628 - 629
• Main Authors: Patil, Ashok D, Freyer, Alan J, Carte, Brad, Taylor, Paul B, Johnson, Randall K, Faulkner, D. John
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.04.2002; Glendale, AZ American Society of Pharmacognosy
• Subjects: Alkaloids - chemistry; Alkaloids - isolation & purification; Alkaloids - pharmacology; Animals; Biological and medical sciences; Cathepsin K; Cathepsins - antagonists & inhibitors; Chromatography, Thin Layer; Cysteine Proteinase Inhibitors - chemistry; Cysteine Proteinase Inhibitors - isolation & purification; Cysteine Proteinase Inhibitors - pharmacology; General pharmacology; Inhibitory Concentration 50; Medical sciences; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Palau; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Porifera - chemistry; Spectrophotometry, Infrared; Spectroscopy, Fourier Transform Infrared; Tryptamines - chemistry; Tryptamines - isolation & purification; Tryptamines - pharmacology; Micronesia; Oceania; Palau; Imidazole derivatives; Cathepsin K; Enzyme; Nitrogen heterocycle; Pharmacognosy; Cysteine endopeptidases; Enzyme inhibitor; Animal origin; In vitro; Biological activity; Marine environment; Peptidases; Alkaloid; Carboline derivatives; Porifera; Bicyclic compound; Hydrolases; Isolation; Aromatic compound; Invertebrata; Structural analysis
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np010500l

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-β-carboline structure of haploscleridamine (1) was elucidated through spectral techniques. Haploscleridamine (1) was found to be an inhibitor of cathepsin K with an IC50 of 26 μM.