Antibacterial activity of synthetic 1,3‐bis(aryloxy)propan‐2‐amines against Gram‐positive bacteria

Abstract

Synthetic 1,3‐bis(aryloxy)propan‐2‐amines have been shown in previous studies to possess several biological activities, such as antifungal and antiprotozoal. In the present study, we describe the antibacterial activity of new synthetic 1,3‐bis(aryloxy)propan‐2‐amines against Gram‐positive pathogens (Streptococcus pyogenes, Enterococcus faecalis and Staphylococcus aureus) including Methicillin–resistant S. aureus strains. Our compounds showed minimal inhibitory concentrations (MIC) in the range of 2.5–10 μg/ml (5.99–28.58 μM), against different bacterial strains. The minimal bactericidal concentrations found were similar to MIC, suggesting a bactericidal mechanism of action of these compounds. Furthermore, possible molecular targets were suggested by chemical similarity search followed by docking approaches. Our compounds are similar to known ligands targeting the cell division protein FtsZ, Quinolone resistance protein norA and the Enoyl‐[acyl‐carrier‐protein] reductase FabI. Taken together, our data show that synthetic 1,3‐bis(aryloxy)propan‐2‐amines are active against Gram‐positive bacteria, including multidrug–resistant strains and can be a promising lead in the development of new antibacterial compounds for the treatment of these infections.

Discovery of a novel and selective fungicide that targets fungal cell wall to treat dermatomycoses: 1,3‐bis(3,4‐dichlorophenoxy)propan‐2‐aminium chloride

“…Structurally, the position of the chlorine is important for improving the antifungal action, since the substitution at positions meta and para of the disubstituted molecule 2j was more advantageous (lower MICs) than the substitution at ortho and para positions as for 2i (Figure ). These results corroborate the finding by Lavorato et al and Serafim et al with some compounds of the same class investigated in this study: for meta ‐substituted compounds, it was observed that the electronic effect of ring substituent has a greater influence on biological activity of this chemical class . One hundred and twenty‐one compounds were analysed in our study to follow the sequence of molecules also tested by our group for antiprotozoal and antibacterial .…”

“…for meta-substituted compounds, it was observed that the electronic effect of ring substituent has a greater influence on biological activity of this chemical class. 23,25 One hundred and twenty-one compounds were analysed in our study to follow the sequence of molecules also tested by our group for antiprotozoal and antibacterial. [23][24][25] This relevant number of synthetic compounds comprised structures of five different chemical classes with varying substituents.…”

“…23,25 One hundred and twenty-one compounds were analysed in our study to follow the sequence of molecules also tested by our group for antiprotozoal and antibacterial. [23][24][25] This relevant number of synthetic compounds comprised structures of five different chemical classes with varying substituents. These structural diversities were very important for the discussion of structure-activity relationship to determine the property or group of the molecule, as well as its respective position that contributed most to the antifungal activity.…”

Design of Organoiron Dendrimers Containing Paracetamol for Enhanced Antibacterial Efficacy

“…We found dendrimers containing paracetamol groups in the outer spheres were more efficient against Gram-positive bacteria and slightly more efficacious compared to dendrimers carrying hydroxyl molecules in the periphery. It is likely that the presence of a terminal paracetamol group was responsible for the observed increase in efficacy in antimicrobial activity of their dendrimers (possibly due to target interactions with the N–H terminal group) [ 32 , 34 , 58 ]. This trend could show the action of primary amines against Gram-positive bacteria, which may also be related to the bacterial membrane permeability.…”

Antimicrobial resistance: A multifaceted problem with multipronged solutions

“…However, purely synthetic antimicrobials as quinolones can also effectively inhibit bacterial pathogen growth. A synthetic approach was followed by Serafim et al, (Serafim et al, ) for synthesizing new 1,3‐bis(arloxy)propan‐2‐amines with biological activity against Gram‐positive pathogens such as Streptococcus pyogenes , Enterococcus faecalis , and S. aureus . By using docking approaches, the authors suggest that their compounds might bind to the cell division protein FtsZ.…”