Bonomo Carmelo, Bonacci Paolo Giuseppe, Bivona Dalida Angela, Mirabile Alessia, Bongiorno Dafne, Nicitra Emanuele, Marino Andrea, Bonaccorso Carmela, Consiglio Giuseppe, Fortuna Cosimo Gianluca, Stefani Stefania, Musso Nicolò
Department of Biomedical and Biotechnological Sciences (BIOMETEC), Università degli Studi di Catania, Via S. Sofia, 89, 95123 Catania, Italy.
Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, ARNAS Garibaldi Hospital, Università degli Studi di Catania, Via Palermo, 95122 Catania, Italy.
Antibiotics (Basel). 2023 Aug 10;12(8):1308. doi: 10.3390/antibiotics12081308.
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 , , , , , and also and , 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.
发现具有抗菌活性的化合物在对抗抗生素耐药性的持续斗争中至关重要。我们开发了两个定量构效关系（QSAR）模型来设计六种新型杂芳基候选药物，并评估了它们对九种美国典型培养物保藏中心（ATCC）菌株的抗菌性能，这些菌株包括……，……，……，……，……，还有……和……，其中许多属于ESKAPE组。我们将已发表研究中先前测试过的化合物PB4与新发现的具有最佳细胞毒性/最低抑菌浓度（MIC）谱的化合物GC-VI-70相结合。通过用五种抗生素（利奈唑胺、庆大霉素、氨苄青霉素、红霉素、利福平和亚胺培南）测试PB4的亚MIC浓度，我们评估了该组合对ATCC菌株的疗效。为了评估这些化合物的细胞毒性，我们对结肠腺癌（CaCo-2）细胞进行了24小时和48小时的3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定。我们单独测试了抗生素以及与PB4联合使用的情况。令人鼓舞的是，PB4降低了GC-VI-70以及各种临床使用抗生素的MIC值。然而，必须注意的是，本研究中所研究的所有化合物均对细胞表现出细胞毒性活性。这些发现突出了将这些化合物与抗生素联合使用以在较低浓度下提高其有效性同时将细胞毒性作用降至最低的潜力。
