Marine natural products

This review covers the literature published in 2014 for marine natural products (MNPs), with 1116 citations (753 for the period January to December 2014) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1378 in 456 papers for 2014), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included

In silico identification of modulators of J domain protein-Hsp70 interactions in Plasmodium falciparum: a drug repurposing strategy against malaria

Plasmodium falciparum is a unicellular, intracellular protozoan parasite, and the causative agent of malaria in humans, a deadly vector borne infectious disease. A key phase of malaria pathology, is the invasion of human erythrocytes, resulting in drastic remodeling by exported parasite proteins, including molecular chaperones and co-chaperones. The survival of the parasite within the human host is mediated by P. falciparum heat shock protein 70s (PfHsp70s) and J domain proteins (PfJDPs), functioning as chaperones-co-chaperones partnerships. Two complexes have been shown to be important for survival and pathology of the malaria parasite: PfHsp70-x-PFE0055c (exported); and PfHsp70-2-PfSec63 (endoplasmic reticulum). Virtual screening was conducted on the drug repurposing library, the Pandemic Response Box, to identify small-molecules that could specifically disrupt these chaperone complexes. Five top ranked compounds possessing preferential binding affinity for the malarial chaperone system compared to the human system, were identified; three top PfHsp70-PfJDP binders, MBX 1641, zoliflodacin and itraconazole; and two top J domain binders, ezetimibe and a benzo-diazepinone. These compounds were validated by repeat molecular dockings and molecular dynamics simulation, resulting in all the compounds, except for MBX 1461, being confirmed to bind preferentially to the malarial chaperone system. A detailed contact analysis of the PfHsp70-PfJDP binders identified two different types of modulators, those that potentially inhibit complex formation (MBX 1461), and those that potentially stabilize the complex (zoliflodacin and itraconazole). These data suggested that zoliflodacin and itraconazole are potential novel modulators specific to the malarial system. A detailed contact analysis of the J domain binders (ezetimibe and the benzo-diazepinone), revealed that they bound with not only greater affinity but also a better pose to the malarial J domain compared to that of the human system. These data suggested that ezetimibe and the benzo-diazepinone are potential specific inhibitors of the malarial chaperone system. Both itraconazole and ezetimibe are FDA-approved drugs, possess anti-malarial activity and have recently been repurposed for the treatment of cancer. This is the first time that such drug-like compounds have been identified as potential modulators of PfHsp70-PfJDP complexes, and they represent novel candidates for validation and development into anti-malarial drugs

Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking

The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry techniques are well-suited to high-throughput characterization of natural products, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social molecular networking (GNPS, http://gnps.ucsd.edu), an open-access knowledge base for community wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of ‘living data’ through continuous reanalysis of deposited data

Author Correction: Single compounds elicit complex behavioural responses in wild, free-ranging rats

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper

The Development of Semiochemical Lures for Invasive Rats: An Integrated Chemical Image and Response-Guided Approach

Olfactory lures are important tools in pest-species management, being widely used to monitor and trap populations. For vertebrates like rats, lures are most commonly foods such as peanut butter. However, these are perishable and require frequent replenishment; factors that decrease control operation efficacy and increase costs. Synthetic semiochemical-based lures might address these limitations, but their identification and use for vertebrate population management remains an underexploited opportunity. We used headspace solid-phase microextraction and gas chromatography-mass spectrometry to characterise the volatile chemical profiles of 19 food products previously presented to wild, free-ranging rats and assessed for attraction. Partial least squares regression identified 10 of the 111 compounds found in two or more analysed products to be statistically significant predictors of attraction. The identity of nine of the compounds was verified using authentic samples, while one was not commercially available. Field trials used tracking tunnels to present compounds at seven different concentrations from 10,000 ppm to 0.01 ppm. Inked cards inside tracking tunnels were used to quantify visitations using species tracking marks, with the presence of rat tracks on inked cards scored to provide a tracking rate. Five compounds outperformed peanut butter while eight individual semiochemical-based lures each statistically outperformed peanut butter. Nearly half of all confirmed visits to compounds were with lures presented at 0.1 and 0.01 ppm. A trend of increasing tracking rates with decreasing lure concentration was identified for aggregated compound data. Our results suggest a number of compounds have the potential for onward development as synthetic attractants for rats. Further, the results support our integrated chemical image and response-guided approach that statistically associated behavioural responses to a range of products with the volatile compounds in those products. This approach has the potential to identify semiochemical compounds, either allelochemical or pheromone, for use as olfactory lures for managing and monitoring a range of vertebrate pest species

New Long-Life Semiochemical Lures for Rats

Olfactory lures are important pest control tools, being widely used to attract animals to detection devices, traps, and poisons. For small mammals, like commensal rodents, almost all lures are foods. For invertebrates, however, semiochemical lures predominate and have done so for decades. Semiochemical lures overcome the inherent limitations of food-based lures, such as their perishability and inconsistent odour properties, and poor performance when foods are abundant. They can also provide benefits like low cost, ease of handling, and in-field longevity. Semiochemical lures for rodents would be a major advance, like that achieved for invertebrate monitoring and control, but their discovery has been constrained by the complexity of the challenge. Our research group is the first to achieve animal response-guided semiochemical lure discovery. We statistically integrated rapid field-based bioassays with scent chemical profiling and partial least squares regression to identify and test a suite of new single- and multi-compound rat lures. Field trials identified a tetrad and dyad mixture as the best performing lures, with an attraction rate of 0.61 and 0.60, respectively, compared to an attraction rate of 0.55 for the peanut butter standard. In total, 17 compound-based lures performed statistically as well as the peanut butter standard. We are currently working with an industry partner to encapsulate the lures as consumable, cost-effective pest-control products. Semiochemical lures will be particularly useful for multi-kill traps, toxic bait delivery devices, and remote monitoring devices that could operate for long periods without intervention. These devices offer substantial control program cost reductions but require long-life lures to realise their full potential

New Long-Life Semiochemical Lures for Rats

Olfactory lures are important pest control tools, being widely used to attract animals to detection devices, traps, and poisons. For small mammals, like commensal rodents, almost all lures are foods. For invertebrates, however, semiochemical lures predominate and have done so for decades. Semiochemical lures overcome the inherent limitations of food-based lures, such as their perishability and inconsistent odour properties, and poor performance when foods are abundant. They can also provide benefits like low cost, ease of handling, and in-field longevity. Semiochemical lures for rodents would be a major advance, like that achieved for invertebrate monitoring and control, but their discovery has been constrained by the complexity of the challenge. Our research group is the first to achieve animal response-guided semiochemical lure discovery. We statistically integrated rapid field-based bioassays with scent chemical profiling and partial least squares regression to identify and test a suite of new single- and multi-compound rat lures. Field trials identified a tetrad and dyad mixture as the best performing lures, with an attraction rate of 0.61 and 0.60, respectively, compared to an attraction rate of 0.55 for the peanut butter standard. In total, 17 compound-based lures performed statistically as well as the peanut butter standard. We are currently working with an industry partner to encapsulate the lures as consumable, cost-effective pest-control products. Semiochemical lures will be particularly useful for multi-kill traps, toxic bait delivery devices, and remote monitoring devices that could operate for long periods without intervention. These devices offer substantial control program cost reductions but require long-life lures to realise their full potential

The Development of Semiochemical Lures for Invasive Rats: An Integrated Chemical Image and Response-Guided Approach

Olfactory lures are important tools in pest-species management, being widely used to monitor and trap populations. For vertebrates like rats, lures are most commonly foods such as peanut butter. However, these are perishable and require frequent replenishment; factors that decrease control operation efficacy and increase costs. Synthetic semiochemical-based lures might address these limitations, but their identification and use for vertebrate population management remains an underexploited opportunity. We used headspace solid-phase microextraction and gas chromatography-mass spectrometry to characterise the volatile chemical profiles of 19 food products previously presented to wild, free-ranging rats and assessed for attraction. Partial least squares regression identified 10 of the 111 compounds found in two or more analysed products to be statistically significant predictors of attraction. The identity of nine of the compounds was verified using authentic samples, while one was not commercially available. Field trials used tracking tunnels to present compounds at seven different concentrations from 10,000 ppm to 0.01 ppm. Inked cards inside tracking tunnels were used to quantify visitations using species tracking marks, with the presence of rat tracks on inked cards scored to provide a tracking rate. Five compounds outperformed peanut butter while eight individual semiochemical-based lures each statistically outperformed peanut butter. Nearly half of all confirmed visits to compounds were with lures presented at 0.1 and 0.01 ppm. A trend of increasing tracking rates with decreasing lure concentration was identified for aggregated compound data. Our results suggest a number of compounds have the potential for onward development as synthetic attractants for rats. Further, the results support our integrated chemical image and response-guided approach that statistically associated behavioural responses to a range of products with the volatile compounds in those products. This approach has the potential to identify semiochemical compounds, either allelochemical or pheromone, for use as olfactory lures for managing and monitoring a range of vertebrate pest species