Tsirogianni Artemis, Kournoutou Georgia G, Mpogiatzoglou Maria, Dinos George, Athanassopoulos Constantinos M
Synthetic Organic Chemistry Laboratory, Department of Chemistry, University of Patras, GR-26504 Patras, Greece.
Department of Biochemistry, School of Medicine, University of Patras, GR-26504 Patras, Greece.
Antibiotics (Basel). 2023 Apr 29;12(5):832. doi: 10.3390/antibiotics12050832.
In a previous study published by our group, successful modification of the antibiotic chloramphenicol (CHL) was reported, which was achieved by replacing the dichloroacetyl tail with alpha and beta amino acids, resulting in promising new antibacterial pharmacophores. In this study, CHL was further modified by linking the basic amino acids lysine, ornithine, and histidine to the primary hydroxyl group of CHL via triazole, carbamate, or amide bonding. Our results showed that while linking the basic amino acids retained antibacterial activity, it was somewhat reduced compared to CHL. However, in vitro testing demonstrated that all derivatives were comparable in activity to CHL and competed for the same ribosomal binding site with radioactive chloramphenicol. The amino acid-CHL tethering modes were evaluated either with carbamate () derivatives, which exhibited higher activity, or with amide- (-) or triazole-bridged compounds (-), which were equally potent. Our findings suggest that these new pharmacophores have potential as antimicrobial agents, though further optimization is needed.
在我们小组之前发表的一项研究中，报告了抗生素氯霉素（CHL）的成功修饰，这是通过用α和β氨基酸取代二氯乙酰尾实现的，从而产生了有前景的新型抗菌药效基团。在本研究中，通过三唑、氨基甲酸酯或酰胺键将碱性氨基酸赖氨酸、鸟氨酸和组氨酸连接到CHL的伯羟基上，对CHL进行了进一步修饰。我们的结果表明，虽然连接碱性氨基酸保留了抗菌活性，但与CHL相比有所降低。然而，体外测试表明，所有衍生物的活性与CHL相当，并与放射性氯霉素竞争相同的核糖体结合位点。用活性较高的氨基甲酸酯（）衍生物或活性相当的酰胺（-）或三唑桥连化合物（-）评估氨基酸-CHL的连接模式。我们的研究结果表明，这些新的药效基团有作为抗菌剂的潜力，不过还需要进一步优化。
