Evaluation of the Effects of Heteroaryl Ethylene Molecules in Combination with Antibiotics: A Preliminary Study on Control Strains
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Published:2023-08-10
Issue:8
Volume:12
Page:1308
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ISSN:2079-6382
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Container-title:Antibiotics
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language:en
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Short-container-title:Antibiotics
Author:
Bonomo Carmelo1ORCID, Bonacci Paolo Giuseppe1ORCID, Bivona Dalida Angela1ORCID, Mirabile Alessia1, Bongiorno Dafne1, Nicitra Emanuele1ORCID, Marino Andrea2ORCID, Bonaccorso Carmela3ORCID, Consiglio Giuseppe3, Fortuna Cosimo Gianluca3, Stefani Stefania1ORCID, Musso Nicolò1ORCID
Affiliation:
1. Department of Biomedical and Biotechnological Sciences (BIOMETEC), Università degli Studi di Catania, Via S. Sofia, 89, 95123 Catania, Italy 2. Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, ARNAS Garibaldi Hospital, Università degli Studi di Catania, Via Palermo, 95122 Catania, Italy 3. Department of Chemical Sciences, Università degli Studi di Catania, Viale Andrea Doria 6, 95125 Catania, Italy
Abstract
The discovery of compounds with antibacterial activity is crucial in the ongoing battle against antibiotic resistance. We developed two QSAR models to design six novel heteroaryl drug candidates and assessed their antibacterial properties against nine ATCC strains, including Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and also Salmonella enterica and Escherichia coli, many of which belong to the ESKAPE group. We combined PB4, a previously tested compound from published studies, with GC-VI-70, a newly discovered compound, with the best cytotoxicity/MIC profile. By testing sub-MIC concentrations of PB4 with five antibiotics (linezolid, gentamycin, ampicillin, erythromycin, rifampin, and imipenem), we evaluated the combination’s efficacy against the ATCC strains. To assess the compounds’ cytotoxicity, we conducted a 24 h and 48 h 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on colorectal adenocarcinoma (CaCo-2) cells. We tested the antibiotics alone and in combination with PB4. Encouragingly, PB4 reduced the MIC values for GC-VI-70 and for the various clinically used antibiotics. However, it is essential to note that all the compounds studied in this research exhibited cytotoxic activity against cells. These findings highlight the potential of using these compounds in combination with antibiotics to enhance their effectiveness at lower concentrations while minimizing cytotoxic effects.
Funder
European Union Italian Ministry of Health Research Program
Subject
Pharmacology (medical),Infectious Diseases,Microbiology (medical),General Pharmacology, Toxicology and Pharmaceutics,Biochemistry,Microbiology
Reference47 articles.
1. The Antibiotic Resistance Crisis;Ventola;Pharm. Ther.,2015 2. Antibiotic Resistance: The Challenges and Some Emerging Strategies for Tackling a Global Menace;Ugwu;J. Clin. Lab. Anal.,2022 3. Pathogenicity and Virulence of Staphylococcus Aureus;Cheung;Virulence,2021 4. Smith, H.Z., and Kendall, B. (2023). StatPearls, StatPearls Publishing. 5. Antimicrobial Resistance: A Global Multifaceted Phenomenon;Prestinaci;Pathog. Glob. Health,2015
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