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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1412797
This article is part of the Research Topic Unveiling the Future of Antibiotics: Exploring the WHO Priority List of Antibiotic-Resistant Bacteria for Discovery, Research, and Development of Novel Therapeutics View all articles

Discovery of new antimicrobial thiophene derivatives with activity against drug-resistant Gram negative-bacteria

Provisionally accepted
Irene M. Panadero Irene M. Panadero 1Marcos Morales Tenorio Marcos Morales Tenorio 2Alfonso García-Rubia Alfonso García-Rubia 2Tiziana Ginex Tiziana Ginex 2Khalil Eskandari Khalil Eskandari 1Ana Martinez Ana Martinez 2Carmen Gil Carmen Gil 2Younes Smani Younes Smani 1*
  • 1 Andalusian Center for Development Biology, Spanish National Research Council (CSIC), Seville, Spain
  • 2 Margarita Salas Center for Biological Research, Spanish National Research Council (CSIC), Madrid, Catalonia, Spain

The final, formatted version of the article will be published soon.

    Our aim is to identify new small molecules with antimicrobial potential, especially against colistin-resistant (Col-R) Acinetobacter baumannii and Escherichia coli. After initial hits identification by fingerprint similarity, MIC of 24 heterocyclic derivatives for A. baumannii and E. coli reference strains, and bactericidal activity of selected thiophenes against Col-R strains were determined. We analyzed changes in bacterial membrane permeability and the OMPs profile. Additionally, we determined bacterial adherence to host cells and performed molecular docking studies to assess their binding to bacterial targets. The compounds' MICs ranged from 4 to >64mg/L. Thiophene derivatives 4, 5 and 8 exhibited MIC50 values between 16 and 32mg/L for Col-R A. baumannii and 8 and 32mg/L for Col-R E. coli. The time-kill curve assay demonstrated that thiophenes 4 and 8 had bactericidal effects against Col-R A. baumannii and E. coli. Furthermore, treatment with them resulted in increased membrane permeabilization and reduced adherence of these isolates to host cells. Finally, the docking studies showed a stronger binding affinity to CarO1 and Omp33 of A. baumannii and OmpW and OmpC of E. coli. These findings indicate that thiophene derivatives possess antibacterial activity against Col-R A. baumannii and E. coli, suggesting that they may enhance the repertoire of drug treatments against bacteria.

    Keywords: new thiophene derivatives, antimicrobial resistant drugs, Treatment, Bacteria, Infection, Gram-negative

    Received: 05 Apr 2024; Accepted: 03 Jul 2024.

    Copyright: © 2024 Panadero, Morales Tenorio, García-Rubia, Ginex, Eskandari, Martinez, Gil and Smani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Younes Smani, Andalusian Center for Development Biology, Spanish National Research Council (CSIC), Seville, Spain

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