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Designing antibacterial Bi(III)-, Ga(III)- and Sb(III)-Thiosemicarbazone complexes to enhance lead compound development

Title: Designing antibacterial Bi(III)-, Ga(III)- and Sb(III)-Thiosemicarbazone complexes to enhance lead compound development
Authors: Scaccaglia M.; Verderi L.; Manini L.; Rega M.; Pinelli S.; Bacci C.; Pelosi G.; Bisceglie F.
Contributors: Scaccaglia, M.; Verderi, L.; Manini, L.; Rega, M.; Pinelli, S.; Bacci, C.; Pelosi, G.; Bisceglie, F.
Publisher Information: Elsevier Inc.
Publication Year: 2026
Collection: Università di Parma: CINECA IRIS
Subject Terms: Antimicrobial resistance; block p metal; Gram negative; quinoline; thiosemicarbazone
Description: The exploration of chemical space is crucial for advancing antibacterial drug discovery and developing novel therapeutic agents. We used a bismuth compound that restores carbapenem sensitivity in NDM-1-producing bacterial strains as a starting point to design a library of compounds through modifications of both the central metal core and ligand structure. The metal was substituted with other p-block metals like gallium(III) and antimony(III), while the ligand, a thiosemicarbazone, was derivatized, yielding a library of 16 compounds for biological evaluation. The synthesized compounds were tested for antimicrobial activity. Synergistic studies with resistant strains identified new lead compounds that restored antibiotic sensitivity. In vivo toxicity using Galleria mellonella larvae showed favorable safety profiles for several compounds. Despite strong in vitro activity, the compounds did not significantly improve survival rates in infected larvae, either as monotherapies or in combination with antibiotics. This study highlights the potential of rational lead compound modifications to identify novel antimicrobial agents.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/wos/WOS:001597250700002; volume:274; journal:JOURNAL OF INORGANIC BIOCHEMISTRY; https://hdl.handle.net/11381/3046973
DOI: 10.1016/j.jinorgbio.2025.113092
Availability: https://hdl.handle.net/11381/3046973; https://doi.org/10.1016/j.jinorgbio.2025.113092
Accession Number: edsbas.366A4B0A
Database: BASE