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

• Published in: Folia microbiologica 2020-04, Vol.65 (2), p.393-405
• Main Authors: Andrade, Jéssica Tauany, Alves, Silmara Lucia Grego, Lima, William Gustavo, Sousa, Carla Daiane Ferreira, Carmo, Lucas Fernandes, De Sá, Nívea Pereira, Morais, Fernanda Barbara, Johann, Susana, Villar, José Augusto Ferreira Perez, Ferreira, Jaqueline Maria Siqueira
• Format: Article
• Language: English
• Subjects: Alcohols; Aldehydes; Alkenes; Antiinfectives and antibacterials; Antimicrobial agents; Applied Microbiology; Biomedical and Life Sciences; Candida; Cell walls; Chemical synthesis; Chitin; Drug resistance; Environmental Engineering/Biotechnology; Fungicides; Glucan; Hydroxybenzaldehydes; Immunology; Life Sciences; Microbiology; Microorganisms; Minimum inhibitory concentration; Nitrogen dioxide; Nosocomial infection; Original Article; Pharmacology; β-Glucan
• ISSN: 0015-5632; 1874-9356
• DOI: 10.1007/s12223-019-00747-7

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 (NO 2 ) 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 ( 4a – 4d ). 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 C andida 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.