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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Synthesis and testing of novel alternative oxidase (AOX) inhibitors with antifungal activity against Moniliophthora perniciosa (Stahel), the causal agent of witches' broom disease of cocoa, and other phytopathogens

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Barsottini, Mario R. O. [1, 2] ; Pires, Barbara A. [2] ; Vieira, Maria L. [1] ; Pereira, Jose G. C. [1] ; Costa, Paulo C. S. [3, 1] ; Sanita, Jaqueline [1] ; Coradini, Alessandro [2] ; Mello, Fellipe [2] ; Marschalk, Cidnei [2] ; Silva, Eder M. [4] ; Paschoal, Daniele [4] ; Figueira, Antonio [4] ; Rodrigues, Fabio H. S. [5] ; Cordeiro, Artur T. [1] ; Miranda, Paulo C. M. L. [3] ; Oliveira, Paulo S. L. [1] ; Sforca, Mauricio L. [1] ; Carazzolle, Marcelo F. [2] ; Rocco, Silvana A. [1] ; Pereira, Goncalo A. G. [2]
Total Authors: 20
[1] Brazilian Ctr Res Energy & Mat, Brazilian Biosci Natl Lab, Campinas, SP - Brazil
[2] Univ Estadual Campinas, Inst Biol, Genom & BioEnergy Lab, Dept Genet Evolut Microbiol & Imunol, Campinas, SP - Brazil
[3] Univ Estadual Campinas, Inst Chem, Dept Organ Chem, Campinas, SP - Brazil
[4] Univ Sao Paulo, Ctr Nucl Energy Agr, Piracicaba - Brazil
[5] Univ Warwick, Sch Life Sci, Gibbet Hill Campus, Coventry, W Midlands - England
Total Affiliations: 5
Document type: Journal article
Source: Pest Management Science; v. 75, n. 5, p. 1295-1303, MAY 2019.
Web of Science Citations: 1

Background Moniliophthora perniciosa (Stahel) Aime \& Phillips-Mora is the causal agent of witches' broom disease (WBD) of cocoa (Theobroma cacao L.) and a threat to the chocolate industry. The membrane-bound enzyme alternative oxidase (AOX) is critical for M. perniciosa virulence and resistance to fungicides, which has also been observed in other phytopathogens. Notably AOX is an escape mechanism from strobilurins and other respiration inhibitors, making AOX a promising target for controlling WBD and other fungal diseases. Results We present the first study aimed at developing novel fungal AOX inhibitors. N-Phenylbenzamide (NPD) derivatives were screened in the model yeast Pichia pastoris through oxygen consumption and growth measurements. The most promising AOX inhibitor (NPD 7j-41) was further characterized and displayed better activity than the classical AOX inhibitor SHAM in vitro against filamentous fugal phytopathogens, such as M. perniciosa, Sclerotinia sclerotiorum and Venturia pirina. We demonstrate that 7j-41 inhibits M. perniciosa spore germination and prevents WBD symptom appearance in infected plants. Finally, a structural model of P. pastoris AOX was created and used in ligand structure-activity relationships analyses. Conclusion We present novel fungal AOX inhibitors with antifungal activity against relevant phytopathogens. We envisage the development of novel antifungal agents to secure food production. (c) 2018 Society of Chemical Industry (AU)

FAPESP's process: 17/17000-4 - Analysis of the interaction Moniliophthora perniciosa x 'Micro-Tom' tomato: non-host type resistance, effects on the development and role of phytohormones in pathogenesis
Grantee:Eder Marques da Silva
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 15/09870-3 - Identification of new inhibitor molecules of “The enzyme alternative oxidase with potential antifungal activity against cocoa pathogens
Grantee:Bárbara Aliende Pires
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 16/10498-4 - Investigation of strategies of adaptation to the pathogenic life style of fungi from the Moniliophthora genus at various levels of biological organizations: species, biotypes, and geographic lineages
Grantee:Antonio Vargas de Oliveira Figueira
Support type: Research Projects - Thematic Grants
FAPESP's process: 15/06677-8 - Metabolic engineering and identification of quantitative traits loci related to HMF tolerance of Saccharomyces cerevisiae strain
Grantee:Fellipe da Silveira Bezerra de Mello
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 15/07653-5 - Discovery and development of new compounds aiming to control Moniliophthora perniciosa, the causal agent of Witches' Broom Disease of cocoa, based on the inhibition of the cellular respiration
Grantee:Gonçalo Amarante Guimarães Pereira
Support type: Regular Research Grants
FAPESP's process: 14/15339-6 - Characterization of the inhibition of the enzyme alternative oxidase (AOX) by aromatic amides and development of high-throughput screening platform to search for novel inhibitors of the AOX from the fungus Moniliophthora perniciosa
Grantee:Mario Ramos de Oliveira Barsottini
Support type: Scholarships in Brazil - Doctorate