We conducted a quantitative and qualitative chemical analysis of cane toad bufadienolides--the cardioactive steroids that are believed to be the principal cane toad toxins. We found complex shifts in toxin composition through toad ontogeny: (1) eggs contain at least 28 dominant bufadienolides, 17 of which are not detected in any other ontogenetic stage; (2) tadpoles present a simpler chemical profile with two to eight dominant bufadienolides; and (3) toxin diversity decreases during tadpole life but increases again after metamorphosis (larger metamorph/juvenile toads display five major bufadienolides). Total bufadienolide concentrations are highest in eggs (2.64 +/- 0.56 micromol/mg), decreasing during tadpole life stages (0.084 +/- 0.060 micromol/mg) before rising again after metamorphosis (2.35 +/- 0.45 micromol/mg). These variations in total bufadienolide levels correlate with toxicity to Australian frog species. For example, consumption of cane toad eggs killed tadpoles of two Australian frog species (Limnodynastes convexiusculus and Litoria rothii), whereas no tadpoles died after consuming late-stage cane toad tadpoles or small metamorphs. The high toxicity of toad eggs reflects components in the egg itself, not the surrounding jelly coat. Our results suggest a dramatic ontogenetic shift in the danger that toads pose to native predators, reflecting rapid changes in the types and amounts of toxins during toad development.

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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.

Summary1. In many anuran species, larvae modify their developmental trajectories and behaviour in response to chemical cues that predict predator risk. Recent reviews highlight a dearth of studies on delayed (post-metamorphic) consequences of larval experience. 2. We raised cane toad ( Bufo marinus ) tadpoles either under control conditions or in the presence of non-lethal predator cues (crushed conspecifics). 3. Exposure to these chemical cues massively reduced size at metamorphosis, as predicted by theory. Parotoid glands were larger relative to body size in post-metamorphic animals from the experimental treatment, suggesting higher investment in chemical defences. 4. Exposure to chemical cues from crushed conspecifics during larval life reduced total bufadienolide content of metamorphs, but increased amounts of one specific bufadienolide (bufalin). 5. Hence, cane toads respond to perceived predation risk in the aquatic environment by metamorphosing at a smaller size and modifying their investment in defensive toxins during post-metamorphic life. 6. Phenotypically flexible responses to larval conditions vary among amphibian taxa, and can involve significant carry-over effects into post-metamorphic life.

An Australian marine-derived isolate of Aspergillus versicolor (MST-MF495) yielded the known fungal metabolites sterigmatocystin, violaceol I, violaceol II, diorcinol, (-)-cyclopenol, and viridicatol, along with a new alkaloid, cottoquinazoline A (1), and two new cyclopentapeptides, cotteslosins A (2) and B (3). Structures for 1-3 and the known compounds were determined by spectroscopic analysis. The absolute configurations of 1-3 were addressed by chemical degradation and application of the C(3) Marfey's method. The use of "cellophane raft" high-nutrient media as a device for up-regulating secondary metabolite diversity in marine-derived fungi is discussed. The antibacterial properties displayed by A. versicolor (MST-MF495) were attributed to the phenols violaceol I, violaceol II, and diorcinol, while cotteslosins 2 and 3 were identified as weak cytotoxic agents.

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-O (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 dehydroambliol-A (47).

Chemical analysis of an Australian marine-derived isolate of Penicillium bilaii, collected from the Huon estuary, Port Huon, Tasmania, yielded the known fungal aromatic polyketides citromycetin (1) and citromycin (2) together with two dihydro analogues, (-)-2,3-dihydrocitromycetin (3) and (-)-2,3-dihydrocitromycin (4). An Australian terrestrial isolate of Penicillium striatisporum collected near Shalvey, New South Wales, also yielded citromycetin (1), citromycin (2), and the new dihydro analogue (-)-2,3-dihydrocitromycetin (3), together with fulvic acid (5), anhydrofulvic acid (6), and a selection of new methoxylated analogues, 12-methoxycitromycetin (7), 12-methoxycitromycin (8), (-)-12-methoxy-2,3-dihydrocitromycetin (9), and 12-methoxyanhydrofulvic acid (10). P. bilaii also yielded the rare siderophore pistillarin (11), the known diketopiperazines cyclo-(L-Phe -L-Pro) (12), cyclo-(L-Pro-L-Tyr) (13), cyclo-(L-Pro-L-Val) (14), and cis-bis(methylthio)silvatin (15), and three new diketopiperazines, bilains A-C (16-18). The structures for the Penicillium metabolites 1- 18 were assigned by a combination of detailed spectroscopic analysis, including correlation with relevant literature data, chemical derivatization, degradation, and biosynthetic considerations. The citromycin polyketides 2 and 4 and the diketopiperazine 15 were weakly cytotoxic.

A Spongosorites sp. collected during trawling operations off the southern coast of Australia returned the new alkaloid dragmacidin E (3), the structure of which was secured by detailed spectroscopic analysis. Dragmacidin E (3), and its co-metabolite dragmacidin D (1) have been identified as potent inhibitors of serine-threonine protein phosphatases.