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1.
PLoS One ; 19(4): e0298813, 2024.
Article in English | MEDLINE | ID: mdl-38630682

ABSTRACT

As place-based conservation organizations, zoos are in a central position to support individuals in making small changes in their lives that will support the protection of wildlife and their habitats. This paper describes the secondary analysis of data collected from multi-phase front-end, exploratory evaluation that informed the development of a conservation action campaign in association with a non-profit, urban zoo. In phase one, internal organization staff were invited to attend workshops during which they brainstormed potential conservation actions that they felt were important for the zoo to promote. They identified and ranked 164 unique actions. In phase two, the ranking was used to narrow down the 164 actions to 20 actions which were used to develop a survey administered to visitors who opted in to receiving online surveys from the zoo. The survey asked participants to state their interest in each of the 20 conservation actions. The Transtheoretical Model of Behavior Change informed the analysis of responses. Through this approach we identified actions that people were already doing, interested in doing, and not interested in doing. The responses from this survey were used to narrow down the list further to 10 actions used in a survey in phase three. This second survey administered to zoo visitors on grounds asked participants which of the 10 actions they would be most interested in doing, and the perceived barriers and benefits of doing them. This process allowed us to use evidence-based decision making to choose which conservation actions would resonate most with the community for our conservation action campaign. We also were able to identify values visitors held that might influence environmentally friendly behaviors. Visitors who responded to this survey tended to respond in ways that aligned with self-transcendent values. The research suggests that the campaign should focus on habitat restoration and remediation and purchasing wildlife friendly coffee and other products.


Subject(s)
Animals, Zoo , Conservation of Natural Resources , Animals , Humans , Surveys and Questionnaires , Animals, Wild , Coffee
2.
Bioorg Med Chem Lett ; 43: 128089, 2021 07 01.
Article in English | MEDLINE | ID: mdl-33964438

ABSTRACT

Several boron-containing small molecules have been approved by the US FDA to treat human diseases. We explored potential applications of boron-containing compounds in modern agriculture by pursuing multiple research and development programs. Here, we report a novel series of multi-substitution benzoxaboroles (1-36), a compound class that we recently reported as targeting geranylgeranyl transferase I (GGTase I) and thereby inhibiting protein prenylation (Kim et al., 2020). These compounds were designed, synthesized, and tested against the agriculturally important fungal pathogens Mycosphaerella fijiensis and Colletotrichum sublineolum in a structure-activity relationship (SAR) study. Compounds 13, 28, 30, 34 and 36 were identified as active leads with excellent antifungal MIC95 values in the range of 1.56-3.13 ppm against M. fijiensis and 0.78-3.13 ppm against C. sublineolum.


Subject(s)
Antifungal Agents/pharmacology , Ascomycota/drug effects , Boron Compounds/pharmacology , Colletotrichum/drug effects , Fungicides, Industrial/pharmacology , Agriculture , Alkyl and Aryl Transferases/antagonists & inhibitors , Alkyl and Aryl Transferases/metabolism , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Ascomycota/metabolism , Boron Compounds/chemical synthesis , Boron Compounds/chemistry , Colletotrichum/metabolism , Dose-Response Relationship, Drug , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/chemistry , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship
3.
ACS Chem Biol ; 15(7): 1930-1941, 2020 07 17.
Article in English | MEDLINE | ID: mdl-32573189

ABSTRACT

Fungal pathogens pose an increasing threat to global food security through devastating effects on staple crops and contamination of food supplies with carcinogenic toxins. Widespread deployment of agricultural fungicides has increased crop yields but is driving increasingly frequent resistance to available agents and creating environmental reservoirs of drug-resistant fungi that can also infect susceptible human populations. To uncover non-cross-resistant modes of antifungal action, we leveraged the unique chemical properties of boron chemistry to synthesize novel 6-thiocarbamate benzoxaboroles with broad spectrum activity against diverse fungal plant pathogens. Through whole genome sequencing of Saccharomyces cerevisiae isolates selected for stable resistance to these compounds, we identified mutations in the protein prenylation-related genes, CDC43 and ERG20. Allele-swapping experiments confirmed that point mutations in CDC43, which encodes an essential catalytic subunit within geranylgeranyl transferase I (GGTase I) complex, were sufficient to confer resistance to the benzoxaboroles. Mutations in ERG20, which encodes an upstream farnesyl pyrophosphate synthase in the geranylgeranylation pathway, also conferred resistance. Consistent with impairment of protein prenylation, the compounds disrupted membrane localization of the classical geranylgeranylation substrate Cdc42. Guided by molecular docking predictions, which favored Cdc43 as the most likely direct target, we overexpressed and purified functional GGTase I complex to demonstrate direct binding of benzoxaboroles to it and concentration-dependent inhibition of its transferase activity. Further development of the boron-containing scaffold described here offers a promising path to the development of GGTase I inhibitors as a mechanistically distinct broad spectrum fungicide class with reduced potential for cross-resistance to antifungals in current use.


Subject(s)
Antifungal Agents/pharmacology , Boron Compounds/pharmacology , Protein Prenylation/drug effects , Saccharomyces cerevisiae Proteins/metabolism , Thiocarbamates/pharmacology , Alkyl and Aryl Transferases/antagonists & inhibitors , Alkyl and Aryl Transferases/genetics , Alkyl and Aryl Transferases/metabolism , Antifungal Agents/chemical synthesis , Antifungal Agents/metabolism , Boron Compounds/chemical synthesis , Boron Compounds/metabolism , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Membrane/drug effects , Dimethylallyltranstransferase/genetics , Dimethylallyltranstransferase/metabolism , Drug Resistance, Fungal/genetics , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/pharmacology , Fungi/drug effects , Fungi/genetics , Molecular Docking Simulation , Point Mutation , Protein Binding , Saccharomyces cerevisiae Proteins/genetics , Thiocarbamates/chemical synthesis , Thiocarbamates/metabolism , cdc42 GTP-Binding Protein, Saccharomyces cerevisiae/metabolism
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