Efficacy of Novel Quaternary Ammonium and Phosphonium Salts Differing in Cation Type and Alkyl Chain Length against Antibiotic-Resistant Staphylococcus aureus

• Type: Article in International Scientific Journal
• Date: 2024

Authors

Nunes, B (Author) Other; Cagide, F (Author) Other; Fernandes, C (Author) Other; Anabela Borges (Author) FEUP; Fernanda Borges (Author) FCUP; Simoes, M (Author) Other; Simões M (Author) FEUP

Journal

Title: International Journal Of Molecular Sciences

Vol. 25

Final page: 504

ISSN: 1661-6596

Publisher: MDPI

Indexing

ISI Web of Knowledge - 12 Citations

Scopus - 12 Citations

Associated Projects

CIQUP - Financiamento Plurianual da Unidade de I&D CIQUP - Centro de Investigação em Química da Universidade do Porto

Biocide_for_Biofilm - Desenvolvimento de novas soluções biocidas para o controlo efetivo de biofilmes

LEPABE - Financiamento Plurianual 2020-2023 da Unidade de I&D LEPABE - Laboratório de Engenharia de Processos, Ambiente, Biotecnologia e Energia

LEPABE - Projeto Estratégico do LEPABE - Laboratório de Engenharia de Processos, Ambiente, Biotecnologia e Energia

ALiCE - ALiCE - Laboratório Associado em Engenharia Química

Other information

Authenticus ID: P-00Z-SVS

DOI: 10.3390/ijms25010504

Abstract (EN): Antibacterial resistance poses a critical public health threat, challenging the prevention and treatment of bacterial infections. The search for innovative antibacterial agents has spurred significant interest in quaternary heteronium salts (QHSs), such as quaternary ammonium and phosphonium compounds as potential candidates. In this study, a library of 49 structurally related QHSs was synthesized, varying the cation type and alkyl chain length. Their antibacterial activities against Staphylococcus aureus, including antibiotic-resistant strains, were evaluated by determining minimum inhibitory/bactericidal concentrations (MIC/MBC) <= 64 mu g/mL. Structure-activity relationship analyses highlighted alkyl-triphenylphosphonium and alkyl-methylimidazolium salts as the most effective against S. aureus CECT 976. The length of the alkyl side chain significantly influenced the antibacterial activity, with optimal chain lengths observed between C-10 and C-14. Dose-response relationships were assessed for selected QHSs, showing dose-dependent antibacterial activity following a non-linear pattern. Survival curves indicated effective eradication of S. aureus CECT 976 by QHSs at low concentrations, particularly compounds 1e, 3e, and 5e. Moreover, in vitro human cellular data indicated that compounds 2e, 4e, and 5e showed favourable safety profiles at concentrations <= 2 mu g/mL. These findings highlight the potential of these QHSs as effective agents against susceptible and resistant bacterial strains, providing valuable insights for the rational design of bioactive QHSs.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 30