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Pharmacologic potential of new nitro-compounds as antimicrobial agents against nosocomial pathogens: design, synthesis, and in vitro effectiveness

  • Jéssica Tauany Andrade
  • Silmara Lucia Grego Alves
  • William Gustavo Lima
  • Carla Daiane Ferreira Sousa
  • Lucas Fernandes Carmo
  • Nívea Pereira De Sá
  • Fernanda Barbara Morais
  • Susana Johann
  • José Augusto Ferreira Perez Villar
  • Jaqueline Maria Siqueira FerreiraEmail author
Original Article
  • 35 Downloads

Abstract

Nosocomial infections are an important cause of morbi-mortality worldwide. The increase in the rate of resistance to conventional drugs in these microorganisms has stimulated the search for new therapeutic options. The nitro moiety (NO2) is an important pharmacophore of molecules with high anti-infective activity. We aimed to synthesize new nitro-derivates and to evaluate their antibacterial and anti-Candida potential in vitro. Five compounds [3-nitro-2-phenylchroman-4-ol (3); 3-nitro-2-phenyl-2H-chromene (4a); 3-nitro-2-(4-chlorophenyl)-2H-chromene (4b); 3-nitro-2-(4-fluorophenyl)-2H-chromene (4c), and 3-Nitro-2-(2,3-dichlorophenyl)-2H-chromene (4d)] were efficiently synthesized by Michael-aldol reaction of 2-hydroxybenzaldehyde with nitrostyrene, resulting in one β-nitro-alcohol (3) and four nitro-olefins (4a4d). The antibacterial and anti-Candida potentials were evaluated by assaying minimal inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and minimum bactericidal concentration (MBC). Mono-halogenated nitro-compounds (4b and 4c) showed anti-staphylococcal activity with MIC values of 15.6–62.5 μg/mL and MBC of 62.5 μg/mL. However, the activity against Gram-negative strains was showed to be considerably lower and our data suggests that this effect was associated with the outer membrane. Furthermore, nitro-compounds 4c and 4d presented activity against Candida spp. with MIC values ranging from 7.8–31.25 μg/mL and MFC of 15.6–500 μg/mL. In addition, these compounds were able to induce damage in fungal cells increasing the release of intracellular material, which was associated with actions on the cell wall independent of quantitative changes in chitin and β-glucan. Together, these findings show that nitro-compounds can be exploited as anti-staphylococcal and anti-Candida prototypes.

Notes

Acknowledgments

JTA and WGL are grateful to UFSJ, CAPES, and FAPEMIG for the master’s and doctor’s scholarship, respectively.

Funding information

Universidade Federal de Sao Joao del-Rei, Conselho Nacional de Desenvolvimento Cientifico and Tecnologico (CNPq), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES) - Finance Code 001, and Fundacao de Amparo a Pesquisa do estado de Minas Gerais (FAPEMIG) provided financial support.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i. 2019

Authors and Affiliations

  • Jéssica Tauany Andrade
    • 1
  • Silmara Lucia Grego Alves
    • 2
  • William Gustavo Lima
    • 1
  • Carla Daiane Ferreira Sousa
    • 1
  • Lucas Fernandes Carmo
    • 2
  • Nívea Pereira De Sá
    • 3
  • Fernanda Barbara Morais
    • 1
  • Susana Johann
    • 3
  • José Augusto Ferreira Perez Villar
    • 2
  • Jaqueline Maria Siqueira Ferreira
    • 1
    Email author
  1. 1.Laboratório de Microbiologia MédicaUniversidade Federal de São João del-Rei (UFSJ)DivinópolisBrazil
  2. 2.Laboratório de Síntese Orgânica e NanoestruturasUniversidade Federal de São João del-Rei (UFSJ) - Campus Centro Oeste Dona LinduDivinópolisBrazil
  3. 3.Departamento de Microbiologia, Instituto de Ciências BiológicasUniversidade Federal de Minas GeraisBelo HorizonteBrazil

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