RESUMEN
Antimicrobial agents 4a-g and 5a-g with very good potency were synthesized with 100% ee from phenylpropanolamine (norephedrine) by BF3 catalyzed three components one pot Mannich reaction in good yields. Obtained compounds were characterized using spectral techniques. Antimicrobial study of these compounds revealed a good to very high potential activity against tested microbes when compared to standard antimicrobial drugs streptomycin and ketoconazole. These synthesized compounds exhibited significant minimum inhibitory concentration (MIC) values against Gram positive and Gram negative bacteria. Amongst compound 4b, 4c, 4d, 4e, 5a, and 5e exhibited very high potent MIC values against tested twelve bacteria and three fungi when compared to control. When subjected to molecular docking, in silico studies revealed significant binding energies ranging from -7.06 to -8.90 kcal/mol for all obtained compounds towards target receptor DNA topoisomerase IV and amongst compounds 4b and 4d have shown maximum binding energies 8.70 and 8.90 kcal/mol, respectively.
Asunto(s)
Antibacterianos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Bases de Mannich/química , Bases de Mannich/farmacología , Simulación del Acoplamiento Molecular , Fenilpropanolamina/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Boranos , Catálisis , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Fenilpropanolamina/síntesis química , Fenilpropanolamina/química , Relación Estructura-ActividadRESUMEN
Enantiomerically pure N-alkylated ß-amino alcohols 1a, 1a', 1c, 1c', 1d, 1d', 1e and 1e', with ee 100% have been synthesized from phenylpropanolamines 2. Effect of the neighboring chiral environment on the newly formed chiral center has been studied experimentally and concluded that the newly formed chiral center's absolute configuration is opposite to the adjacent (α- or ß-) chiral environment. The antimicrobial activity of the synthesized ß-amino alcohols were screened using in vitro disc diffusion method and variable antimicrobial activities were shown for 1a, 1a', 1c, 1c', 1d, 1d', 1e &1e' and amongst them 1d &1d' exhibited significant activity against bacteria and fungi. In silico studies revealed all the synthesized ß-amino alcohols 1a-e and 1a'-e' have shown good binding energies ranging from -7.38 to -6.09 kJ/mol towards the target receptor DNA topoisomerase IV and 1d' has shown maximum binding energy -7.38 kJ/mol.