Design, synthesis, antibacterial activity, and in vivo safety evaluation of novel phloroglucinol triacetate tris(imidazolium) salts.

Authors

Ameer S Al-Mayali, Ahmed Hassoon Mageed

Published in

RSC advances. Aug 20, 2026. Epub Aug 20, 2026.

Abstract

A series of novel phloroglucinol triacetate tris(imidazolium) salts were synthesized and evaluated for their antimicrobial efficacy, hemocompatibility, antioxidant effects, and in vivo toxicity. The synthetic route involved the initial acylation of phloroglucinol with chloroacetyl chloride in the presence of triethylamine to afford tris(chloroacetate) intermediate, followed by nucleophilic substitution with N-alkylimidazole derivatives to produce the target salts in good yields (68-79%). All compounds were fully characterized by FTIR, NMR, and mass spectrometry. The biological evaluation revealed that compounds 3 and 5 exhibited promising antibacterial activity against both Gram-positive and Gram-negative bacteria. Compound 3 demonstrated the highest potency, with minimum inhibitory concentration (MIC) values of 7.8 µg mL^-1 against S. aureus and 31.25 µg mL^-1 against E. coli. The superior activity of compound 3 was attributed to its favorable balance of lipophilicity and cationic charge density, facilitating efficient interaction with bacterial membranes. Hemolysis assays performed at concentrations ranging from 50 to 250 µg mL^-1 indicated low hemolytic activity for compounds 2 and 3, suggesting selective antimicrobial action with minimal damage to mammalian erythrocytes. The in vivo antioxidant assessment in rats demonstrated that compound 2 maintained near-normal levels of glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT), indicating minimal oxidative stress and superior biocompatibility. Histopathological examination further supported its safety profile, as liver and kidney tissues showed nearly normal architecture with intact hepatocytes, hepatic cords, glomeruli, and renal tubules. Compound 3 induced only mild hepatic and renal alterations, including limited inflammatory infiltration and slight tubular degeneration, without significant disruption of tissue organization or organ function. In general, the synthesized tris(imidazolium) salts demonstrated promising antibacterial activity with low toxicity. Compound 3 showed the highest antimicrobial potency, while compound 2 exhibited preliminary biocompatibility, making this scaffold a promising candidate for the development of new antibacterial agents.

PMID:
42625600
Bibliographic data and abstract were imported from PubMed on 21 Aug 2026.

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