Potent cytotoxic peptides from the Australian marine sponge Pipestela candelabra.

Two consecutive prefractionated fractions of the Australian marine sponge extract, Pipestela candelabra, were identified to be selectively active on the human prostate cancer cells (PC3) compared to the human neonatal foreskin fibroblast non-cancer cells (NFF). Twelve secondary metabolites were isolated in which four compounds are new small peptides. Their structures were characterized by spectroscopic and chemical analysis.

Solid-phase synthesis of Biotin-S-Farnesyl-L-Cysteine, a surrogate substrate for isoprenylcysteine Carboxylmethyltransferase (ICMT).

Inhibition of isoprenylcysteine Carboxylmethyltransferase (ICMT) is of particular interest as a potential target for the development of cancer chemotherapeutic agents. Screening for inhibitors of ICMT utilises a scintillation proximity assay (SPA) in which Biotin-S-Farnesyl-L-Cysteine (BFC) acts as a surrogate substrate. A solid-phase synthesis protocol for the preparation of BFC using 2-chlorotrityl chloride resin as a solid support has been developed to provide sufficient supply of BFC for high throughput screening (HTS) and subsequent chemistry campaigns to target inhibitors of ICMT.

7',8'-Dihydroobolactone, a typanocidal alpha-pyrone from the rainforest tree Cryptocarya obovata.

Mass-directed isolation of the CH(2)Cl(2)/MeOH extract from the leaves of Cryptocarya obovata resulted in the purification of a new trypanocidal alpha-pyrone, 7',8'-dihydroobolactone (1). The chemical structure of 1 was determined by 1D/2D NMR, MS and CD data analysis. 7',8'-Dihydroobolactone was shown to inhibit Trypanosoma brucei brucei with an IC(50) of 2.

The functional antagonist Met-RANTES: a modified agonist that induces differential CCR5 trafficking.

CC chemokine receptor 5 (CCR5) is a pro-inflammatory chemokine receptor that is expressed on cells of the immune system, and specializes in cell migration in response to inflammation and tissue damage. Due to its key role in cell communication and migration, this receptor is involved in various inflammatory and autoimmune diseases, in addition to HIV infection. Met-RANTES is a modified CCR5 ligand that has previously been shown to antagonize CCR5 activation and function in response to its natural ligands in vitro.

(-)-Dibromophakellin: an alpha2B adrenoceptor agonist isolated from the Australian marine sponge, Acanthella costata.

Bioassay-guided fractionation of the organic extract from the marine sponge Acanthella costata resulted in the isolation of the known natural product, (-)-dibromophakellin (1). Using a fluorescence imaging plate reader (FLIPR) based assay, compound 1 was identified as displaying agonist activity against the alpha(2B) adrenoceptor, with an EC(50) of 4.2muM.

Prenylated dihydrochalcones from Boronia bipinnata that inhibit the malarial parasite enzyme target hemoglobinase II.

High-throughput screening of a plant and marine invertebrate extract library to find natural products that inhibit the malarial parasite enzyme target hemoglobinase II led to the isolation of two new active prenylated chalcones, bipinnatones A (1) and B (2), from aerial parts of the Queensland shrub Boronia bipinnata. Their structures were assigned from interpretation of 2D NMR and high-resolution ESIMS data. Compounds 1 and 2 inhibited hemoglobinase II with IC 50 values of 64 and 52 microM, respectively.

Small-molecule inhibitors of the cancer target, isoprenylcysteine carboxyl methyltransferase, from Hovea parvicalyx.

Isoprenylcysteine carboxyl methyltransferase (Icmt) is enzyme target in anticancer drug discovery. An Icmt natural product high-throughput screening campaign was conducted and a hit extract from the roots of Hovea parvicalyx was identified. 2'-Methoxy-3'-prenyl-licodione and 2'-methoxy-3',3''-diprenyl-licodione, two prenylated beta-hydroxychalcone compounds, together with the known flavanone (S)-glabrol, were isolated and identified as bioactive constituents.

Aplysamine 6, an alkaloidal inhibitor of Isoprenylcysteine carboxyl methyltransferase from the sponge Pseudoceratina sp.

The anticancer target isoprenylcysteine carboxyl methyltransferase (Icmt) was the focus of a natural product high-throughput screening campaign. The Australian marine sponge Pseudoceratina sp. yielded aplysamine 6, a new bromotyrosine derivative with an alpha,beta-unsaturated amide linkage, as the bioactive constituent.

Lysianadioic acid, a carboxypeptidase B inhibitor from Lysiana subfalcata.

A new natural product, lysianadioic acid, was isolated from the plant Lysiana subfalcata as a carboxypeptidase B (CPB) inhibitor. It is a potent inhibitor of CPB with an IC(50) of 0.36 microM.

Spermatinamine, the first natural product inhibitor of isoprenylcysteine carboxyl methyltransferase, a new cancer target.

Isoprenylcysteine methyltransferase (Icmt) catalyzes the carboxyl methylation of oncogenic proteins in the final step of a series of post-translational modifications. The inhibition of Icmt provides an attractive and novel anticancer target. A natural product high-throughput screening campaign was conducted to discover inhibitors of Icmt.

Vanillic acid derivatives from the green algae Cladophora socialis as potent protein tyrosine phosphatase 1B inhibitors.

A novel vanillic acid derivative (1) and its sulfate adduct (2) were isolated from a green algae, Cladophora socialis. The structures of 1 and 2 were elucidated from NMR and HRESIMS experiments. Both compounds showed potent inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), an enzyme involved in the regulation of insulin cell signaling.

Axinellamines A-D, Novel Imidazo-Azolo-Imidazole Alkaloids from the Australian Marine Sponge Axinella sp.

Four imidazo-azolo-imidazole alkaloids, axinellamines A-D, have been isolated from an Australian marine sponge, Axinella sp. (order: Halichondrida: family: Axinellidae). These compounds contain a unique perhydrocyclopenta-imidazo-azolo-imidazole carbon skeleton.