2. Academic Validation
  3. Synthesis and anti-ureolitic activity of Biginelli adducts derived from formylphenyl boronic acids

Synthesis and anti-ureolitic activity of Biginelli adducts derived from formylphenyl boronic acids

  • Bioorg Chem. 2024 Nov:152:107735. doi: 10.1016/j.bioorg.2024.107735.
Nathália Evelyn Morais Costa 1,  Pedro Henrique Costa Dos Santos 1,  Victorya Gabryelle Silva Medeiros 2,  Ari Souza Guimarães 2,  Josué Carinhanha Caldas Santos 2,  Nathalia Monteiro Lins Freire 3,  Júlio Cosme Santos da Silva 4,  Thiago Mendonça de Aquino 3,  Luzia V Modolo 5,  Eduardo E Alberto 1,  Ângelo de Fátima 6
Affiliations

Affiliations

  • 1 Grupo de Estudos em Química Orgânica e Biológica (GEQOB), Departamento de Química, ICEx, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
  • 2 Laboratório de Instrumentação e Desenvolvimento em Química Analítica, LINQA, Instituto de Químico e Biotecnologia, 57072-900 Maceió, AL, Brazil.
  • 3 Research Group on Therapeutic Strategies - GPET, Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceió, AL, Brazil.
  • 4 Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceió, AL, Brazil.
  • 5 Departamento de Botânica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • 6 Grupo de Estudos em Química Orgânica e Biológica (GEQOB), Departamento de Química, ICEx, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil. Electronic address: adefatima@qui.ufmg.br.
PMID: 39213798 DOI: 10.1016/j.bioorg.2024.107735
Abstract

Urease is a metalloenzyme that contains two Ni(II) ions in its active site and catalyzes the hydrolysis of urea into ammonia and carbon dioxide. The development of effective urease inhibitors is crucial not only for mitigating nitrogen losses in agriculture but also for offering an alternative treatment against infections caused by resistant pathogens that utilize urease as a virulence factor. This study focuses on synthesizing and investigating the urease inhibition potential of Biginelli Adducts bearing a boric acid group. An unsubstituted or hydroxy-substituted boronic group in the Biginelli adducts structure enhances the urease inhibitory activity. Biophysical and kinetics studies revealed that the best Biginelli adduct (4e; IC50 = 132 ± 12 µmol/L) is a mixed inhibitor with higher affinity to the urease active site over an allosteric one. Docking studies confirm the interactions of 4e with residues essential for urease activity and demonstrate its potential to coordinate with the nickel atoms through the oxygen atoms of carbonyl or boronic acid groups. Overall, the Biginelli adduct 4e shows great potential as an additive for developing enhanced efficiency fertilizers and/or for medical applications.

Keywords

Biginelli adducts; Biophysical and kinetics studies; Boron; Docking studies; Helicobacter pylori; Urea; Urease inhibitors.

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