Antimicrobial Activity and Toxicity of Newly Synthesized 4-[4-(benzylamino)butoxy]-9H-carbazole Derivatives

Abstract

One of the main challenges of medicinal chemistry is the search for new substances with antimicrobial potential that could be used in the fight against pathogenic microorganisms. Therefore, the antimicrobial activity of newly synthesized compounds is still being investigated. Carbazole-containing compounds appear to be promising antibacterial, antifungal, and antiviral agents. The aim of this study was to examine the antimicrobial potential and toxicity of newly synthesized isomeric fluorinated 4-[4-(benzylamino)butoxy]-9H-carbazole derivatives. Their antimicrobial activity against bacteria and fungi was tested according to CLSI guidelines. Similarly to previously studied carbazole-containing compounds, the tested derivatives showed the ability to effectively inhibit the growth of Gram-positive bacteria. The addition of carbazole derivatives 2, 4, and 8 at the concentration of 16 µg/mL caused the inhibition of S. aureus growth by over 60%. The MIC value of compounds 2–5 and 7–10 was 32 µg/mL for Staphylococcus strains. Gram-negative strains of E. coli and P. aeruginosa were found to be more resistant to the tested carbazole derivatives. E. coli cells treated with compounds 3 and 8 at a concentration of 64 µg/mL resulted in a greater-than-40% reduction in bacterial growth. In the case of the P. aeruginosa strain, all compounds in the highest concentration that we tested limited growth by 35–42%. Moreover, an over-60% inhibition of fungal growth was observed in the cultures of C. albicans and A. flavus incubated with 64 µg/mL of compounds 2 or 7 and 1 or 4, respectively. The hemolysis of red blood cells after their incubation with the tested carbazole derivatives was in the range of 2–13%. In the case of human fibroblast cells, the toxicity of the tested compounds was higher. Derivative 1, functionalized with fluorine in position 2 and its hydrobromide, was the least toxic. The obtained results indicated the antimicrobial potential of the tested 4-[4-(benzylamino)butoxy]-9H-carbazole derivatives, especially against S. aureus strains; therefore, it is worth further modifying these structures, in order to enhance their activity against pathogenic microorganisms.