Evaluation of the Effects of Heteroaryl Ethylene Molecules in Combination with Antibiotics: A Preliminary Study on Control Strains

• Main Authors: Carmelo Bonomo (Author), Paolo Giuseppe Bonacci (Author), Dalida Angela Bivona (Author), Alessia Mirabile (Author), Dafne Bongiorno (Author), Emanuele Nicitra (Author), Andrea Marino (Author), Carmela Bonaccorso (Author), Giuseppe Consiglio (Author), Cosimo Gianluca Fortuna (Author), Stefania Stefani (Author), Nicolò Musso (Author)
• Format: Book
• Published: MDPI AG, 2023-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 <i>Enterococcus faecalis</i>, <i>Staphylococcus aureus</i>, <i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i>, <i>Pseudomonas aeruginosa</i>, and also <i>Salmonella enterica</i> and <i>Escherichia coli</i>, 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.

Item Description

10.3390/antibiotics12081308
2079-6382