Robert J. Capon

Exploitation of an ant chemical alarm signal by the zodariid spider Habronestes bradleyi Walckenaer

Intraspecific signals are vulnerable to exploitation by predators that are not the targets of the signal. This cost has been documented for several acoustic, visual and chemical signals, but not for chemical alarm pheromones. We reveal a novel form of exploitation of an ant alarm pheromone by the cursorial spider Habronestes bradleyi (Zodariidae), a specialist predator of the highly territorial and aggressive meat ant Iridomyrmex purpureus. We demonstrate experimentally that H. bradleyi locates I. purpureus workers engaged in territorial interactions with conspecifics, by using the alarm pheromone of the ants as a cue. The spiders are attracted to an airborne cue, identified as the alarm pheromone 6-methyl-5-hepten-2-one, which is produced by injured or alarmed I. purpureus workers but not by inactive l. purpureus, or injured workers of other sympatric ant species. These data demonstrate a novel cost of producing alarm pheromones.

Naseseazines A and B: A New Dimeric Diketopiperazine Framework from a Marine-Derived Actinomycete, Streptomyces sp.

Chemical analysis of a Streptomyces sp. (CMB-MQ030) isolated from a Fijian marine sediment yielded two new diketopiperazines, naseseazines A and B (1, 2), featuring a new dimeric framework. Structures were determined by detailed spectroscopic analysis and C(3) Marfeys analysis.

Abyssomicins from the South China Sea deep-sea sediment Verrucosispora sp.: natural thioether michael addition adducts as antitubercular prodrugs

Tuberculosis (TB) is a leading cause of death in the world today, and is exacerbated by the prevalence of multi- (MDR-TB), extensively (XDR-TB), and totally (TDR-TB) drug resistant strains. Despite the threat to human health, existing frontline TB therapeutics remain constrained to a handful of vintage antibiotics prescribed in a combinatorial format to achieve efficacy. The current shortfall in antitubercular drugs demands urgent attention, to develop new antibiotics effective against all strains of tuberculosis.

Nocardioazines: a novel bridged diketopiperazine scaffold from a marine-derived bacterium inhibits P-glycoprotein.

An Australian marine sediment-derived isolate, Nocardiopsis sp. (CMB-M0232), yielded a new class of prenylated diketopiperazine, indicative of the action of a uniquely regioselective diketopiperazine indole prenyltransferase. The bridged scaffold of nocardioazine A proved to be a noncytotoxic inhibitor of the membrane protein efflux pump P-glycoprotein, reversing doxorubicin resistance in a multidrug resistant colon cancer cell.

Mimicry of host cuticular hydrocarbons by salticid spider Cosmophasis bitaeniata that preys on larvae of tree ants Oecophylla smaragdina.

The salticid spider Cosmophasis bitaeniata preys on the larvae of the green tree ant Oecophylla smaragdina. Gas chromatography (GC) and gas chromatography–mass spectrometry (GC-MS) reveal that the cuticle of C. bitaeniata mimics the mono- and dimethylalkanes of the cuticle of its prey. Recognition bioassays with extracts of the cuticular hydrocarbons of ants and spiders revealed that foraging major workers did not respond aggressively to the extracts of the spiders or conspecific nestmates, but reacted aggressively to conspecific nonnestmates. Typically, the ants either failed to react (as with control treatments with no extracts) or they reacted nonaggressively as with conspecific nestmates. These data indicate that the qualitative chemical mimicry of ants by C. bitaeniata allows the spiders to avoid detection by major workers of O. smaragdina.

Lamellarin-s: A New Aromatic Metabolite from an Australian Tunicate, Didenemnum sp.

An Australian tunicate Didemnum sp. has yielded a new alkaloid lamellarin-S (1) along with the known compound lamellarin-K (12). Of this structure class, lamellarin-S (1) is the first example that demonstrates atropisomerism , and its structure was secured by spectroscopic analysis.

Staurosporines Disrupt Phosphatidylserine Trafficking and Mislocalize Ras Proteins

Background: Ras proteins must be plasma membrane-localized for biological activity. Results: A high content screen identified staurosporines as inhibitors of Ras plasma membrane localization and K-Ras signal transmission by disrupting endosomal recycling of phosphatidylserine. Conclusion: Staurosporines are novel inhibitors of phosphatidylserine trafficking. Significance: Ras trafficking pathways and Ras spatiotemporal organization on the plasma membrane are valid targets for anti-Ras drug development. Oncogenic mutant Ras is frequently expressed in human cancers, but no anti-Ras drugs have been developed. Since membrane association is essential for Ras biological activity, we developed a high content assay for inhibitors of Ras plasma membrane localization. We discovered that staurosporine and analogs potently inhibit Ras plasma membrane binding by blocking endosomal recycling of phosphatidylserine, resulting in redistribution of phosphatidylserine from plasma membrane to endomembrane. Staurosporines are more active against K-Ras than H-Ras. K-Ras is displaced to endosomes and undergoes proteasomal-independent degradation, whereas H-Ras redistributes to the Golgi and is not degraded. K-Ras nanoclustering on the plasma membrane is also inhibited. Ras mislocalization does not correlate with protein kinase C inhibition or induction of apoptosis. Staurosporines selectively abrogate K-Ras signaling and proliferation of K-Ras-transformed cells. These results identify staurosporines as novel inhibitors of phosphatidylserine trafficking, yield new insights into the role of phosphatidylserine and electrostatics in Ras plasma membrane targeting, and validate a new target for anti-Ras therapeutics.

Fossil Steranes with Unprecedented Methylation in Ring-a

Abstract Steranes with an additional methyl group at position 3β- or 2α-, and which have no presently known biogenic precursors, have been shown to occur in some ancient sediments and petroleums by GC-MS comparison with synthetic standards.

The luffarins (A-Z), novel terpenes from an Australian marine sponge, Luffariella geometrica

A marine sponge, Luffariella geometrica Kirkpatrick, collected from the southern Australian coastal waters of the Great Australian Bight, has been found to contain 14 new bicyclic sesterterpenes, luffarin-A (14), -B (15), -C (16), -D (17), -E (18), -F (19), -G (20), -H (21), -I (22), -J (23), -K (24), -L (25), -M (26) and -N (27), a new bicyclic bisnorsesterterpene, luffarin-0 (30), a new monocyclic sesterterpene, luffarin-P (32), six new acyclic sesterterpenes, luffarin-Q (35), -R (36), -S (37), -T (38), -U (39) and -V (40), two new diterpenes, luffarin-W (41) and -X (44), and two new bisnorditerpenes luffarin-Y (45) and -Z (46). These novel marine metabolites have been assigned structures, including stereochemistry, on the basis of detailed spectroscopic analysis, chemical correlation, derivatization, and biosynthetic considerations. Studies directed at the absolute stereochemistry of the luffarins have also permitted assignment of absolute stereochemistry to the known marine natural products (E)-neomanoalide (3), (Z)-neomanoalide (4) and dehydroarnbliol-A (47).

The trikentrins : novel indoles from the sponge trikentrion flabelliforme

Abstract Five new indoles, cis -trikentrin A (1), trans -trikentrin A (2), trans -trikentrin B (3), cis -trikentrin B (4) and iso - trans -trikentrin B (5), were isolated from the marine sponge Trikentrion flabelliforme . All possess antimicrobial activity and were identified by detailed spectroscopic analysis.