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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.)

N-Phenylbenzamide derivatives as alternative oxidase inhibitors: Synthesis, molecular properties, H-1-STD NMR, and QSAR

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Costa, Paulo C. S. [1] ; Barsottini, Mario R. O. [2, 3] ; Vieira, Maria L. L. [4] ; Pires, Barbara A. [2] ; Evangelista, Joel S. [1] ; Zeri, Ana C. M. [5] ; Nascimento, Andrey F. Z. [5] ; Silva, Jaqueline S. [4] ; Carazzolle, Marcelo F. [2] ; Pereira, Goncalo A. G. [2] ; Sforca, Mauricio L. [4] ; Miranda, Paulo C. M. L. [1] ; Rocco, Silvana A. [4]
Total Authors: 13
[1] Univ Estadual Campinas, UNICAMP, Inst Chem, BR-13083970 Campinas, SP - Brazil
[2] Univ Estadual Campinas, UNICAMP, Inst Biol, Lab Genom & BioEnergy, BR-13083862 Campinas, SP - Brazil
[3] Univ Sussex, Biochem & Biomed, Falmer BN1 9QG - England
[4] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, BR-13083970 Campinas, SP - Brazil
[5] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Synchrotron Light Lab LNLS, BR-13083970 Campinas, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Source: Journal of Molecular Structure; v. 1208, MAY 15 2020.
Web of Science Citations: 0

In the present work, 117 N-phenylbenzamides (NPDs) were prepared and evaluated against recombinant AOX from the fungal pathogen Moniliophthora perniciosa. H-1, C-13 NMR, FTIR, and mass spectra provided structural information on NPDs. The library compounds were tested as Alternative Oxidase inhibitors in two different assays using the model yeast Pichia pastoris: cell growth and oxygen consumption assays. The most active compound, 3(FH), was further characterized by DRX and 1H-NMR-STD. Single crystal X-ray diffraction showed intra- and intermolecular interactions of 3(FH) in solid-state and elucidated its 3D structural configuration. 1H-NMR-STD allowed us to derive protein-ligand interactions in a membranemimetic system and evidenced an outstanding interaction of 3(FH) with this enzyme. Results of both biological assays were used as input to Quantitative Structure-Activity Relationship models, which highlighted the more important molecular fragments contributions for protein-ligand interaction. (C) 2020 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 18/03130-6 - Investigation of the metabolic alterations of the fungus Moniliophthora perniciosa, causer of the witch s broom of cacao, related to the resistence to antifungal agents inhibiting the enzyme oxidase alternative
Grantee:Bárbara Aliende Pires
Support type: Scholarships in Brazil - Master
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: 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
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