# Assessment of antimicrobial activity of [1,2,4]triazolo[4, 3-a]quinoxaline derivatives individually and in combination with levofloxacin

## TL;DR

This study evaluates new antimicrobial compounds and their combination with levofloxacin to treat bacterial infections more effectively.

## Contribution

The paper introduces new triazoloquinoxaline derivatives with synergistic effects when combined with levofloxacin.

## Key findings

- Compounds 5b, 5d, and 5h showed moderate antimicrobial activity against various bacteria and fungi.
- Combination therapy reduced the required dose of levofloxacin and showed synergy against resistant isolates.
- Field-emission scanning electron microscopy confirmed bacterial cell damage from the combination therapy.

## Abstract

The need to develop new and effective antimicrobial compounds has become a fundamental requirement of the therapeutic system worldwide. In this study, a series of synthetic 4-amino triazoloquinoxaline derivatives were designed and synthesized. The chemical structure of these compounds was confirmed using spectroscopic methods (1H-NMR, 13C-NMR, FT-IR, and MS). Their antimicrobial activity against several Gram-positive and Gram-negative bacteria was then evaluated. The results of biological experiments showed that the synthetic compounds 5b, 5d, and 5h derivatives have moderate antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans compared to some standard drugs. Non-toxic compounds were selected based on MTT and hemolysis assays, and their synergistic effect in combination with levofloxacin (LEV) was investigated. The findings confirmed the effectiveness of combination therapy in reducing the dose of LEV, compounds 5d and 5h against S. aureus and S. epidermidis, as well as 5d and 5b against resistant isolates of MRSA and P. aeruginosa, respectively, with a fractional inhibitory concentration index ≤ 0.5. Field-emission scanning electron microscopy confirmed the complete damage of S. aureus, S. epidermidis, and P. aeruginosa following exposure to the combination therapy of compounds 5b, 5d, and 5h with LEV. This new synergistic therapy has the potential to be used as a novel approach of treating infectious diseases after future investigations.

The online version contains supplementary material available at 10.1038/s41598-026-39141-y.