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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

Grant number: 14/15339-6
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2015
Effective date (End): January 31, 2019
Field of knowledge:Biological Sciences - Biochemistry - Enzymology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Gonçalo Amarante Guimarães Pereira
Grantee:Mario Ramos de Oliveira Barsottini
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated scholarship(s):17/12852-2 - Testing of novel AOX inhibitors targeted at the cacao pathogen Monoliophthora perniciosa, BE.EP.DR


Moniliophthora perniciosa is the fungal pathogen that causes the witches' broom disease of cocoa and accounts for a great decline in the production of cocoa beans in Brazil. In spite of M. perniciosa's great economic and social importance, an effective method to control this pathogen is yet to be developed. M. perniciosa withstands one of the most broadly used class of fungicides, strobilurins, fact that was attributed to the existence of the mitochondrial enzyme Alternative Oxidase (MpAox). After a research initiative aimed at developing novel Aox inhibitors suitable for use as agrochemicals, it was found that some molecules such as aromatic amides might fit this purpose. In this regard, the objective of this research project is to explore the role of these aromatic amides as Aox inhibitors, through the employment of biochemical-based assays with purified MpAox. Furthermore, these assays will be adapted to suit High-Throughput Screening requirements, which in turn will bring about the opportunity to screen a large number of compounds in search for novel MpAox inhibitors. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BARSOTTINI, MARIO R. O.; COPSEY, ALICE; YOUNG, LUKE; BARONI, RENATA M.; CORDEIRO, ARTUR T.; PEREIRA, GONCALO A. G.; MOORE, ANTHONY L. Biochemical characterization and inhibition of the alternative oxidase enzyme from the fungal phytopathogen Moniliophthora perniciosa. COMMUNICATIONS BIOLOGY, v. 3, n. 1 MAY 25 2020. Web of Science Citations: 2.
COSTA, PAULO C. S.; BARSOTTINI, MARIO R. O.; VIEIRA, MARIA L. L.; PIRES, BARBARA A.; EVANGELISTA, JOEL S.; ZERI, ANA C. M.; NASCIMENTO, ANDREY F. Z.; SILVA, JAQUELINE S.; CARAZZOLLE, MARCELO F.; PEREIRA, GONCALO A. G.; SFORCA, MAURICIO L.; MIRANDA, PAULO C. M. L.; ROCCO, SILVANA A. N-Phenylbenzamide derivatives as alternative oxidase inhibitors: Synthesis, molecular properties, H-1-STD NMR, and QSAR. Journal of Molecular Structure, v. 1208, MAY 15 2020. Web of Science Citations: 1.
BARSOTTINI, MARIO R. O.; PIRES, BARBARA A.; VIEIRA, MARIA L.; PEREIRA, JOSE G. C.; COSTA, PAULO C. S.; SANITA, JAQUELINE; CORADINI, ALESSANDRO; MELLO, FELLIPE; MARSCHALK, CIDNEI; SILVA, EDER M.; PASCHOAL, DANIELE; FIGUEIRA, ANTONIO; RODRIGUES, FABIO H. S.; CORDEIRO, ARTUR T.; MIRANDA, PAULO C. M. L.; OLIVEIRA, PAULO S. L.; SFORCA, MAURICIO L.; CARAZZOLLE, MARCELO F.; ROCCO, SILVANA A.; PEREIRA, GONCALO A. G. 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. Pest Management Science, v. 75, n. 5, p. 1295-1303, MAY 2019. Web of Science Citations: 1.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
BARSOTTINI, Mario Ramos de Oliveira. Rational design of inhibitors of the mitochondrial enzyme alternative oxidase (AOX) with fungicide activity against Moniliophthora perniciosa, causal agent of the witches' broom disease of cocoa. 2019. 96 f. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia.

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