Isolation of steroidal glycosides from the Caribbean sponge Pandaros acanthifolium.

Four new steroidal glycosides, acanthifoliosides G-J (1-4), were isolated as minor constituents from the Caribbean marine sponge Pandaros acanthifolium. These metabolites are characterized by a highly oxygenated D ring and the presence of a disaccharide rhamnose-glucose residue and a rhamnose at positions C-3 and C-15, respectively. Their structures were established on the basis of extensive interpretation of 1D and 2D NMR data and HRESIMS analyses.

Evaluation of pseudopteroxazole and pseudopterosin derivatives against Mycobacterium tuberculosis and other pathogens.

Pseudopterosins and pseudopteroxazole are intriguing marine natural products that possess notable antimicrobial activity with a commensurate lack of cytotoxicity. New semi-synthetic pseudopteroxazoles, pseudopteroquinoxalines and pseudopterosin congeners along with simple synthetic mimics of the terpene skeleton were synthesized. In order to build structure-activity relationships, a set of 29 new and previously reported compounds was assessed for in vitro antimicrobial and cytotoxic activities.

One-pot syntheses of pseudopteroxazoles from pseudopterosins: a rapid route to non-natural congeners with improved antimicrobial activity.

Rapid one-pot methodologies to prepare pseudopteroxazole (1) and novel congeners from abundant natural pseudopterosins have been devised. This is highlighted here with the first synthesis of the marine natural product homopseudopteroxazole (2) utilizing a novel, silver(I)-mediated catechol to benzoxazole transformation. Pseudopteroxazoles and isopseudopteroxazoles exhibit potent activity against a range of important Gram-positive pathogens including Mycobacterium spp.

Marine diterpene glycosides.

Marine diterpene glycosides (MDGs) respresent a small but highly significant group of the much larger class of marine diterpenes. The three well-studied examples of MDGs are eleutherobins, pseudopterosins and fuscosides, all of which exhibit extremely promising biological activity. The eleutherobins are potent anti-mitotic agents, and the pseudopterosins and fuscosides are potent anti-inflammatory agents.

Carteriosulfonic acids A-C, GSK-3beta inhibitors from a Carteriospongia sp.

Modulators of Wnt signaling have therapeutic potential in a number of human diseases. A fractionated library from marine invertebrates was screened in a luciferase assay designed to identify modulators of Wnt signaling. A fraction from a Carteriospongia sp.

Psammaplin A as a general activator of cell-based signaling assays via HDAC inhibition and studies on some bromotyrosine derivatives.

The Wnt signaling pathway regulates cell growth and development in metazoans, and is therefore of interest for drug discovery. By screening a library of 5808 pre-fractionated marine extracts in a cell-based Wnt signaling assay, several signaling activators and inhibitors were observed. LCMS-based fractionation rapidly identified an active compound from Pseudoceratina purpurea as psammaplin A, a known HDAC inhibitor.

Fractionated marine invertebrate extract libraries for drug discovery.

The high-throughput screening and drug discovery paradigm has necessitated a change in preparation of natural product samples for screening programs. In an attempt to improve the quality of marine natural products samples for screening, several fractionation strategies were investigated. The final method used HP20SS as a solid support to effectively desalt extracts and fractionate the organic components.