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Research Article Open access CC BY 4.0

Tranexamic Acid-Phenol Smart Scaffolds with Imine Linker: Unlocking Antimicrobial Potential Through In Vitro and In Silico Insights

Jovana S. Dragojević, Žiko Milanović, Kristina Milisavljević, Nevena Petrović, Jelena Petronijević, Nenad Joksimović, Vera M. Divac, Marijana Kosanić, Marina D. Kostić

Organics · pp. 54–54 · Published 16 Dec 2025

10.3390/org6040054

Abstract

A novel series of Schiff bases (3a–3k), incorporating tranexamic acid (TXA) and phenol-derived aldehydes via imine linkers, was synthesized and structurally characterized. The antimicrobial activity of the compounds was evaluated against a range of clinically and environmentally relevant bacterial and fungal strains. Among them, derivatives 3i and 3k, bearing bromine and chlorine substituents on the phenol ring, exhibited the most potent antimicrobial effects, particularly against Penicillium italicum and Proteus mirabilis (MIC as low as 0.014 mg/mL). To elucidate the underlying mechanism of action, in silico molecular docking studies were conducted, revealing strong binding affinities of 3i and 3k toward fungal sterol 14α-demethylase (CYP51B), with predicted binding energies surpassing those of the reference antifungal ketoconazole. Additionally, UV-Vis and fluorescence spectroscopy assays demonstrated good stability of compound 3k in PBS and its effective binding to human serum albumin (HSA), respectively. ADMET and ProTox-II predictions further supported the drug-likeness, low toxicity (Class 4), and favorable pharmacokinetic profile of compound 3k. Collectively, these findings highlight TXA–phenol imine derivatives as promising scaffolds for the development of next-generation antimicrobial agents, particularly targeting resistant fungal pathogens.

Chemistry Antimicrobial In silico Combinatorial chemistry In vitro Moiety Imine Biochemistry

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