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New antibiotics to fight multiresistent bacteria

A study led by Younes Smani, researcher at the Andalusian Center for Developmental Biology and professor of Microbiology at the UPO, focuses on the discovery of new thiophene derivatives as effective antimicrobial agents against Acinetobacter baumannii and Escherichia coli infections.

A recent experimental research study has discovered new antibiotics effective against the multidrug-resistant bacteria Acinetobacter baumannii and Escherichia coli, two of the microorganisms highlighted by the World Health Organization (WHO) as priorities for the development of new treatments due to their ability to acquire antimicrobial resistance.

This breakthrough, led by Professor Younes Smani, principal investigator of the 'Bacterial Infections' group at the Andalusian Center for Developmental Biology (CABD) and professor of the Microbiology Area of the Pablo de Olavide University (UPO), has been made in collaboration with Dr. Carmen Gil and Dr. Ana Martinez, principal investigators of the 'Medical Chemistry and Translational Biology' group of the Margarita Salas Biological Research Center (CIB-CSIC).



The team from Smani's lab

The work, published in the scientific journal Frontiers in Pharmacology, offers a potential solution to the growing antimicrobial resistance of these bacteria, a problem that both the WHO and various European institutions have described as critical. Antimicrobial resistance has thus become one of the greatest threats to global health, as it is estimated that by 2050 it could cause up to ten million deaths per year if new treatments are not developed, surpassing the figures for cancer mortality. In this scenario, for Dr. Younes Smani it is crucial to develop new treatments: “To address this threat, it is imperative to develop innovative antimicrobial strategies, such as drug repositioning in combination with the few clinically relevant antibiotics”.
An innovative approach: anticancer-derived compounds

In a previous study, Younes Smani's team identified tamoxifen, a drug used in cancer treatments, as a potential antimicrobial agent against Acinetobacter baumannii and Escherichia coli infections. In this most recent research, scientists have used both tamoxifen and its related compound, raloxifene, as a starting point for developing a new series of antibiotics.

Through similarity screening using topological indices and the MBC library, which has more than 3,000 molecules, the researchers were able to identify 27 thiophene derivatives, of which three compounds showed high antibiotic potential against multidrug-resistant strains of these bacteria. “We used chemoinformatics techniques to identify prototypes that we optimized following a medicinal chemistry strategy, thus obtaining thiophene derivatives that have proven to be effective antimicrobials in microbiological assays,” explain Drs. Carmen Gil and Ana Martínez.



Carmen Gil and Ana Martínez of the CIB, authors of the study.

The compounds identified in this work have been patented and are available for licensing by companies interested in developing these new antibiotics.

International collaboration and scientific synergies

This breakthrough has been possible thanks to the collaboration between Younes Smani's teams and that of Carmen Gil and Ana Martínez, facilitated by EU-OPENSCREEN, the European Research Infrastructure (ERIC) dedicated to drug discovery and biological chemistry. The synergy between the two research groups has allowed combining expertise in medicinal chemistry and microbiology, achieving important advances in the field of antimicrobial resistance that has been declared a major threat to global health by world leaders meeting at the UN General Assembly on September 26, 2024.

Molina-Panadero I, Morales-Tenorio M, García-Rubia A, Ginex T, Eskandari K, Martinez A, Gil C, Smani Y. Discovery of new antimicrobial thiophene derivatives with activity against drug-resistant Gram negative-bacteria. Front Pharmacol. 2024 Aug 20;15:1412797. doi: 10.3389/fphar.2024.1412797.

This press release was written in collaboration with the Communications department from UPO.