Evaluation of the Effects of Heteroaryl Ethylene Molecules in Combination with Antibiotics: A Preliminary Study on Control Strains
Carmelo Bonomo,
Paolo Giuseppe Bonacci,
Dalida Angela Bivona,
Alessia Mirabile,
Dafne Bongiorno,
Emanuele Nicitra,
Andrea Marino,
Carmela Bonaccorso,
Giuseppe Consiglio,
Cosimo Gianluca Fortuna,
Stefania Stefani,
Nicolò Musso
Affiliations
Carmelo Bonomo
Department of Biomedical and Biotechnological Sciences (BIOMETEC), Università degli Studi di Catania, Via S. Sofia, 89, 95123 Catania, Italy
Paolo Giuseppe Bonacci
Department of Biomedical and Biotechnological Sciences (BIOMETEC), Università degli Studi di Catania, Via S. Sofia, 89, 95123 Catania, Italy
Dalida Angela Bivona
Department of Biomedical and Biotechnological Sciences (BIOMETEC), Università degli Studi di Catania, Via S. Sofia, 89, 95123 Catania, Italy
Alessia Mirabile
Department of Biomedical and Biotechnological Sciences (BIOMETEC), Università degli Studi di Catania, Via S. Sofia, 89, 95123 Catania, Italy
Dafne Bongiorno
Department of Biomedical and Biotechnological Sciences (BIOMETEC), Università degli Studi di Catania, Via S. Sofia, 89, 95123 Catania, Italy
Emanuele Nicitra
Department of Biomedical and Biotechnological Sciences (BIOMETEC), Università degli Studi di Catania, Via S. Sofia, 89, 95123 Catania, Italy
Andrea Marino
Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, ARNAS Garibaldi Hospital, Università degli Studi di Catania, Via Palermo, 95122 Catania, Italy
Carmela Bonaccorso
Department of Chemical Sciences, Università degli Studi di Catania, Viale Andrea Doria 6, 95125 Catania, Italy
Giuseppe Consiglio
Department of Chemical Sciences, Università degli Studi di Catania, Viale Andrea Doria 6, 95125 Catania, Italy
Cosimo Gianluca Fortuna
Department of Chemical Sciences, Università degli Studi di Catania, Viale Andrea Doria 6, 95125 Catania, Italy
Stefania Stefani
Department of Biomedical and Biotechnological Sciences (BIOMETEC), Università degli Studi di Catania, Via S. Sofia, 89, 95123 Catania, Italy
Nicolò Musso
Department of Biomedical and Biotechnological Sciences (BIOMETEC), Università degli Studi di Catania, Via S. Sofia, 89, 95123 Catania, Italy
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.