AGROCHEMICAL BIODISCOVERY - Can be defined as the search for bioactive natural products that inform and inspire the development of new animal health and/or crop protection products, to improve and replace those that have become less effective, and support the treatment of a wide array of commercially significant animal/crop diseases.


Successful agrochemicals support the farming sector and allied communities, enhancing productivity and economic returns, while protecting the environment, and guaranteeing food security. As with pharmaceuticals, agrochemical discovery is critically dependent on access to diverse, high quality molecules. A poor choice of chemistry leads to no new agrochemicals!

Our agrochemical biodiscovery research is a logical extension of expertise in marine and microbial biodiscovery, and can be broadly categorized under the headings of Animal Health and Crop Protection

Animal Health. In this research we seek to discover new natural product-inspired agrochemicals that can be used to treat livestock infections, in particular multidrug resistant (MDR) gastrointestinal parasites. Anthelmintics are agrochemicals that kill or otherwise interrupt the life cycle of pathogenic heminths, worm-like organisms belonging to the phylum Nematoda. While the majority of helminths are free-living aquatic or soil species, numerous species are animal parasites, including heart, lung, kidney, whip, round and hook worms. For example, the nematode
Haemonchus contortus is a serious problem in the livestock industry, infecting and compromising animal health and productivity by attaching to the stomach lining and feeding on blood. Heavily infected livestock (i.e. sheep) become anemic, while severe infections can be life-threatening. For many years the agrochemical market relied on three classes of vintage anthelmintic, the benzimidazoles, imidazothiazoles and macrolactones. The first benzimidazole (thiabendazole) was released in the 1960s, the first imidazothiazole (levamisole) in 1966, and the first macrolactone (Ivermectin®) in 1981. Although these three anthelmintic classes successfully serviced the animal health market for many decades (through an array of closely related products), drug resistance eventually eroded their value. To combat drug resistance the market initially resorted to dual and triple action combination drenches. At first successful, the efficacy of combination drenches rapidly diminished as increasing numbers of animals (and pastures) became infected with MDR nematodes. The rise of MDR is an inevitable consequence of the nematode life-cycle, as infected sheep fertilize pastures with faeces rich in nematode eggs, which hatch, develop to larvae, and are ingested during grazing leading to re-infection.  As drenching does not address infection burden in pastures, the continued cycle of drenching and re-infection ultimately leads to MDR. MDR is an extremely serious problem that has lead to the quarantining of both livestock and pastures, increasing transactional costs, impacting productivity and food security, and leaving agricultural exporters such as Australia particularly vulnerable. There is a compelling case for discovering new anthelmintics effective against MDR nematodes.

To support our efforts in anthelmintic discovery we have partnered with leading animal health companies (Eli Lilly, Elanco, Novartis), and have established an inhouse capability to run the industry gold standard Larval Development Assay (LDA). 


Larval Development Assay (LDA): Nematode infected sheep fitted with fecal collection bags provide a weekly supply of fresh fecal material (~500 g) rich in nematode eggs. Fresh fecal material is shipped to IMB and processed within 24 h to yield nematode eggs (~500,000), which are immediately dispensed to 96 well plates, where they are treated with chemical extracts, fractions and/or pure metabolites, and incubated for 7 days. Over this period eggs hatch, and the larvae develop through L1-L3 life stages. Inspection under a light microscope can detect nematocidal activity at any phase of the nematode life cycle (i.e. ovicides vs larvacides). Skilled operators can visually interpret larvae morphology to differentiate known anthelmintic mechanisms of action (e.g. glutamate chloride channel receptor paralysis), with potency being quantified by serial dilution. Authentic standards of commercial anthemintics are used both as positive controls, and to validate the MDR status of different egg batches. 

Crop Protection. In this collaborative research we seek to discover new approaches to controlling pathogenic infections in crops, more specifically by using of natural product chemical cues produced by rhizosphere bacteria to stimulate biochemical changes in plant pathogens that in turn activate the plant innate immune system. While clearly within the brief of our Agrochemical Biodiscovery program, this research overlaps heavily with our
Chemical Ecology program.

While it should come as no surprise that our most exciting Agrochemical Biodiscovery achievements remain commercial-in-confidence, outlined below a several examples of our published achievements.

(see Banner Images for chemical structures).

Echinobetaines – Water soluble small molecular weight alkaloids isolated from a marine sponge, Echinodictyum sp., collected during scientific trawling operations in the Great Australian Bight, Australia, the echinobetaines exhibit promising anthelmintic activity. A structure activity relationship investigation of the echinobetaine pharmacophore was supported by the total synthesis of echinobetaines A and B, and analogues.

(J. Nat. Prod., 2005, 68, 179-182)

​(Org. Biomol. Chem., 2005, 3, 118-122)

Thiocyanatins – First-in-class lipid bisthiocyanates isolated from a marine sponge, Oceanapia sp., collected during scientific trawling operations off the Northern Rottnest Shelf, Western Australia, the thiocyanatins exhibit excellent anthelmintic activity. A structure activity relationship investigation of the thiocyanatin pharmacophore was supported by the total synthesis of thiocyanatin A, and analogues.

(J. Nat. Prod., 2004, 67, 1277-1282)

(J. Org. Chem., 2001, 66, 7765-7769)

Amphilactams – Macrolactone polyketides bearing an unprecedented acylated examine lactic moiety, isolated from a marine sponge, Amphimedon sp., collected during scientific trawling operations in the Great Australian Bight, Australia. The amphilactams exhibit excellent anthelmintic activity and structure activity investigations were supported by synthetic studies.

(J. Org. Chem., 1999, 64, 1140-1144)

Geodin A Mg salt – A polyketide macrolactam tetramic acid that exists as a stable dimeric magnesium salt, isolated from a marine sponge, Geodia sp., collected during scientific trawling operations in the Great Australian Bight, Australia. Geodin A Mg salt exhibits promising anthelmintic activity. Knowledge of geode A Mg salt prompted the observation that other natural products belonging to this structure class may also occur a natural Mg salts, however, a structural characteristic that is readily lost on exposure to acid conditions during extraction, isolation and/or handling.

(J. Nat. Prod., 1999, 62, 1256-1259)

Notheians – Tetrahydrofuran lipids isolated from an intertidal epiphytic brown alga, Notheia anomala, selected notheians exhibit promising anthelmintic activity. Investigations into the notheian pharmacophore were supported by the isolation and identification of >30 natural notheians, including mono, bis, tri, tetra and pent epoxides, by mechanistic studies and biomimetic synthesis, and by extensive structural activity relationship studies.

(Tetrahedron, 1998, 58, 2227-2245)


Phoriospongins – Depsipeptides isolated from duplicate specimens of Phoriospongia sp. collected by hand in shallow waters of Port Phillip Bay, Victoria, and from a specimen of Callyspongia bilamellata collected during scientific trawling operations in deep waters of the Great Australian Bight, Australia, exhibit promising nematocidal activity.

(J. Nat. Prod., 2002, 65, 358-363)