# Molecular Periphery Design Allows Control of the New Nitrofurans Antimicrobial Selectivity

## TL;DR

Researchers designed new nitrofuran compounds with controlled antimicrobial selectivity, showing strong activity against ESKAPE bacteria and tuberculosis.

## Contribution

The study introduces a molecular periphery design strategy to enhance antimicrobial selectivity and efficacy of new nitrofuran derivatives.

## Key findings

- Some compounds showed similar or lower MICs against ESKAPE pathogens compared to standard antibiotics.
- Compound 2h inhibited S. aureus more effectively than ciprofloxacin, nitrofurantoin, and furazidin.
- Compound 2e was active against Gram-positive ESKAPE pathogens and M. tuberculosis.

## Abstract

A series of 13 new 3-substituted 5-(5-nitro-2-furyl)-1,2,4-oxadiazoles was synthesized from different aminonitriles. All compounds were screened in the disc diffusion test at a 100 μg/mL concentration to determine the bacterial growth inhibition zone presence and diameter, and then the minimum inhibitory concentrations (MICs) were determined for the most active compounds by serial dilution. The compounds showed antibacterial activity against ESKAPE bacteria, predominantly suppressing the growth of 5 species out of the panel. Some compounds had similar or lower MICs against ESKAPE pathogens compared to ciprofloxacin, nitrofurantoin, and furazidin. In particular, 3-azetidin-3-yl-5-(5-nitro-2-furyl)-1,2,4-oxadiazole (2h) inhibited S. aureus at a concentration lower than all comparators. Compound 2e (5-(5-nitro-2-furyl)-3-[4-(pyrrolidin-3-yloxy)phenyl]-1,2,4-oxadiazole) was active against Gram-positive ESKAPE pathogens as well as M. tuberculosis. Differences in the molecular periphery led to high selectivity for the compounds. The induced-fit docking (IFD) modeling technique was applied to in silico research. Molecular docking results indicated the targeting of compounds against various nitrofuran-associated biological targets.