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

Author(s):Show less -

dos Santos, Melina Cardoso ; Tairum, Carlos Abrunhosa ; Montanhero Cabrera, Vitoria Isabela ; Guimaraes Cauz, Ana Carolina ; Ribeiro, Luiz Fernando ; Toledo Junior, Jose Carlos ; Toyama, Marcos Hikari ; Ghilardi Lago, Joao Henrique ; Brocchi, Marcelo ; Soares Netto, Luis Eduardo ; de Oliveira, Marcos Antonio

• Document type: Journal article
• Source: Chemical Research in Toxicology; v. N/A, p. 12-pg., 2022-05-10.

Abstract

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. (AU)

• FAPESP's process: 17/06263-4 - Evaluation of bioactive molecules as inhibitors for atioxidant system of typical 2-Cys peroxiredoxins (AhpC) in baceria
• Grantee: Melina Cardoso dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/19942-7 - Search for inhibitors of the peroxirredoxin system from pathogens and humans
• Grantee: Marcos Antonio de Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/12628-8 - AhpC from Salmonella typhimurium and Staphylococcus aureus: investigation of the inhibitory potential of Adenantine on bacterial peroxiredoxins
• Grantee: Camila Perussi Inácio
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 17/20291-0 - Characterization of the proinflammatory activity of a new serine protease (cdtsp-2) purified from the total venom of Crotalus durissus terrificus
• Grantee: Marcos Hikari Toyama
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/00209-3 - Investigation of molecular interactions between AhpC from Staphylococcus epidermidis with organic hydroperoxides and inhibitors
• Grantee: Luiz Fernando Ribeiro
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 20/02868-1 - Effects of natural compounds over the peroxidase activity of AhpCs and pathogenic bacteria survival
• Grantee: Vitória Isabela Montanhero Cabrera
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC