Heterocyclic chemistry meets wound care: novel p-methyl-m-trifluoromethyl-phenyl-substituted pyrrol-2-one derivatives with antimicrobial and antibiofilm activity.

Authors

Ioana C Marinas, Alina Nicolescu, Cristina M Al-Matarneh, Rafaela Vrabie, Sergiu Shova, Mihaela Silion, Mădălina-Diana Gaboreanu, Miruna Stan, Mariana C Chifiriuc, Mariana Pinteala

Published in

RSC advances. Aug 07, 2026. Epub Aug 07, 2026.

Abstract

Biofilm-associated infections represent a major challenge in the treatment of antimicrobial-resistant pathogens, particularly in chronic and wound-related infections where bacterial adherence and persistence reduce therapeutic efficacy. To address this issue, we report a rapid, economical, and efficient one-pot three-component synthesis of 19 novel bis(trifluoromethyl)-dimethyl-substituted dihydro-pyrrol-2-one derivatives, providing a promising scaffold for the development of new antimicrobial and anti-biofilm agents. The structures of the synthesized compounds were confirmed by NMR, FT-IR, MALDI-MS, and X-ray diffraction analyses. ADMET prediction revealed highly similar pharmacokinetic profiles across the series, supporting the suitability of this scaffold for further medicinal chemistry optimization. Biological evaluation demonstrated that antimicrobial activity was strongly influenced by the nature of the substituents. Compounds 4i, 4j, 4l, 4n, 4o, 4p, and 4t exhibited the highest activity against Staphylococcus aureus, while compounds 4o and 4s were particularly effective against Pseudomonas aeruginosa. Importantly, most derivatives significantly inhibited microbial adherence, highlighting their potential to prevent biofilm formation. Furthermore, all compounds exhibited low hemolytic activity (<5%), and more than 70.59% displayed acceptable cytocompatibility. Among the series, compounds 4i, 4l, and 4s showed the most favorable biological profile, combining potent antimicrobial activity with good compatibility toward HaCaT keratinocytes and blood cells. These findings identify bis(trifluoromethyl)-dimethyl-substituted dihydro-pyrrol-2-ones as promising candidates for the development of novel therapeutics targeting biofilm-associated and drug-resistant infections.

PMID:
42568943
Bibliographic data and abstract were imported from PubMed on 08 Aug 2026.

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