RESUMEN
With the aim of finding new chemical entities selective for fish pathogens to avoid drug resistance in humans, a series of coumarin-chalcone hybrid compounds with different patterns of substitution were designed and synthesized. Their antibacterial activity was evaluated against important types of human bacteria strains (Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa) and against a fourteen strains of the marine pathogen Tenacibaculum maritimum, responsible for tenacibaculosis in fish, which is an important disease that causes great economical loss in the aquaculture industry. All the amino derivatives 5-12 presented high activity against different strains of T. maritimum, no activity against any of the three human pathogenic bacteria strains and no toxicity. Compounds 6, 7 and 11 were the most promising molecules. The most sensitive strains to these compounds were LL01 8.3.8 and LL01 8.3.1, being compound 11 up to 20 times more active than enrofloxacin. Therefore these scaffolds are good candidates for aquaculture treatments, avoiding possible drug resistance problems in humans.
Asunto(s)
Antibacterianos/síntesis química , Chalcona/química , Cumarinas/química , Diseño de Fármacos , Animales , Antibacterianos/química , Antibacterianos/farmacología , Acuicultura , Escherichia coli/efectos de los fármacos , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/prevención & control , Peces , Infecciones por Flavobacteriaceae/microbiología , Infecciones por Flavobacteriaceae/prevención & control , Infecciones por Flavobacteriaceae/veterinaria , Humanos , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Tenacibaculum/efectos de los fármacos , Tenacibaculum/aislamiento & purificaciónRESUMEN
A new series of amino/nitro-substituted 3-arylcoumarins were synthesized and their antibacterial activity against clinical isolates of Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) was evaluated. Some of these molecules exhibited antibacterial activity against S. aureus comparable to the standards used (oxolinic acid and ampicillin). The preliminary structure-activity relationship (SAR) study showed that the antibacterial activity against S. aureus depends on the position of the 3-arylcoumarin substitution pattern. With the aim of finding the structural features for the antibacterial activity and selectivity, in the present manuscript different positions of nitro, methyl, methoxy, amino and bromo substituents on the 3-arylcoumarin scaffold were reported.
Asunto(s)
Aminas/química , Antibacterianos/síntesis química , Antibacterianos/farmacología , Cumarinas/síntesis química , Cumarinas/farmacología , Nitrocompuestos/química , Antibacterianos/química , Cumarinas/química , Dicumarol/síntesis química , Dicumarol/química , Dicumarol/farmacología , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Novobiocina/síntesis química , Novobiocina/química , Novobiocina/farmacología , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
The dramatic worldwide increase of dangerous infections by resistant and multi-resistant microbes makes the search of new molecules and new chemical entities an important topic in Medicinal Chemistry. As the ideal drug candidate has not been attained, an intensive search for new and innovative antimicrobials is still needed. A small series of 3-amino/nitrocoumarins without substitutions or substituted by methyl or methoxy groups at different positions were synthesized and evaluated for their antibacterial and antifungal activities against clinical isolates of Staphylococcus aureus, Escherichia coli and Candida albicans strains. Some of these structurally simple molecules exhibited antibacterial activity. The preliminary SAR study showed that the antibacterial activity against E. coli and S. aureus was dependent on the kind and position of the substitution pattern at the coumarin moiety.