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Adenanthin Is an Efficient Inhibitor of Peroxiredoxins from Pathogens, Inhibits Bacterial Growth, and Potentiates Antibiotic Activities

2022; American Chemical Society; Volume: 36; Issue: 4 Linguagem: Inglês

10.1021/acs.chemrestox.2c00049

1520-5010

Melina Cardoso dos Santos, Carlos A. Tairum, Vitoria Isabela Montanhero Cabrera, Ana Carolina Guimarães Cauz, Luiz Fernando Ribeiro, José Carlos Toledo, Marcos Hikari Toyama, João Henrique G. Lago, Marcelo Brocchi, Luís Eduardo Soares Netto, Marcos Antônio de Oliveira,

Enzyme function and inhibition

The emergence and re-emergence of bacterial strains resistant to multiple drugs represent a global health threat, and the search for novel biological targets is a worldwide concern. AhpC are enzymes involved in bacterial redox homeostasis by metabolizing diverse kinds of hydroperoxides. In pathogenic bacteria, AhpC are related to several functions, as some isoforms are characterized as virulence factors. However, no inhibitor has been systematically evaluated to date. Here we show that the natural ent-kaurane Adenanthin (Adn) efficiently inhibits AhpC and molecular interactions were explored by computer assisted simulations. Additionally, Adn interferes with growth and potentializes the effect of antibiotics (kanamycin and PMBN), positioning Adn as a promising compound to treat infections caused by multiresistant bacterial strains.