Phytochemicals and quaternary phosphonium ionic liquids: Connecting the dots to develop a new class of antimicrobial agents

• Type: Article in International Scientific Journal
• Date: 2023

Authors

Chavarria, D (Author) Other; Anabela Borges (Author) FEUP; Benfeito, S (Author) Other; Sequeira, L (Author) Other; Ribeiro, M (Author) Other; Oliveira, C (Author) Other; Borges, F (Author) Other; Simões, M (Author) Other; Cagide, F (Author) Other; Simões M (Author) FEUP

Journal

Title: Journal of Advanced Research

Vol. 54

Pages: 251-269

ISSN: 2090-1232

Publisher: Cairo University

Indexing

ISI Web of Knowledge - 5 Citations

ISI Web of Science

Scopus - 7 Citations

Associated Projects

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

ABFISH - Desenvolvimento de novos antibióticos para aquacultura

Other information

Authenticus ID: P-00Y-1JV

DOI: 10.1016/j.jare.2023.02.004

Abstract (EN): Introduction: The infections by multidrug-resistant bacteria are a growing threat to human health, and the efficacy of the available antibiotics is gradually decreasing. As such, new antibiotic classes are urgently needed. Objectives: This study aims to evaluate the antimicrobial activity, safety and mechanism of action of phytochemical-based triphenylphosphonium (TPP') conjugates. Methods: A library of phytochemical-based TPP' conjugates was repositioned and extended, and its antimicrobial activity was evaluated against a panel of Gram-positive (methicillin-resistant Staphylococcus aureus - MRSA) and Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii) and fungi (Candida albicans, Cryptococcus neoformans var. grubii). The compounds' cytotoxicity and haemolytic profile were also evaluated. To unravel the mechanism of action of the best compounds, the alterations in the surface charge, bacterial membrane integrity, and cytoplasmic leakage were assessed. Results: Structure-activity-toxicity data revealed the contributions of the different structural components (phenolic ring, carbon-based spacers, carboxamide group, alkyl linker) to the compounds' bioactivity and safety. Dihydrocinnamic derivatives 5 m and 5n stood out as safe, potent and selective antibacterial agents against S. aureus (MIC < 0.25 lg/mL; CC50 > 32 lg/mL; HC10 > 32 lg/mL). Mechanistic studies sug- gest that the antibacterial activity of compounds 5 m and 5n may result from interactions with the bac- terial cell wall and membrane. Conclusions: Collectively, these studies demonstrate the potential of phytochemical-based TPP+ conju- gates as a new class of antibiotics. (c) 2023 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 19