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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: 1

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: 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 Opportunities: Research Projects - Thematic Grants
FAPESP's process: 18/03130-6 - Investigation of the metabolic alterations of the fungus Moniliophthora perniciosa, causal agent of the Witches' broom disease of cacao, related to the resistence to antifungal agents inhibiting the enzyme oxidase alternative
Grantee:Bárbara Aliende Pires
Support Opportunities: 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 Opportunities: 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 Opportunities: Scholarships in Brazil - Doctorate