Kanis Emily, Parks Jessica, Austin Daniel L
School of Pharmacy, Lake Erie College of Osteopathic Medicine, 1858 West Grandview Boulevard, Erie, Pennsylvania 16509, United States.
ACS Pharmacol Transl Sci. 2022 Dec 5;6(1):88-91. doi: 10.1021/acsptsci.2c00168. eCollection 2023 Jan 13.
Cephalosporins are a widely used subclass of β-lactam antibiotics that demonstrate variable protein binding independent of generation or antibiotic coverage. Prior work analyzed carbon 3 (C3) and carbon 7 (C7) substituents (locations of R and R groups respectively) for protein binding interactions. This study builds upon these results with statistical analysis of additional agents of the class. Chemical structures of 23 cephalosporins were used to identify the presence of 40 functional groups, and correlative relationships were identified using established protein binding data. Four functional groups were significantly correlated with protein binding: tetrazole (positive association), pyridinium, primary amine, and quaternary amine (negative associations). Cephalosporins with a negative charge at physiological pH were associated with increased protein binding. Analysis of tetrazole-containing cephalosporins and ceftriaxone indicates the need for further study of the potential role in protein binding of neutral or negatively charged aromatic nitrogen heterocycles linked at the C3 position by a thiomethylene group.
头孢菌素是一类广泛使用的β-内酰胺抗生素，其蛋白结合率各不相同，与药物代数或抗菌谱无关。先前的研究分析了碳3（C3）和碳7（C7）取代基（分别为R和R基团的位置）与蛋白结合的相互作用。本研究在这些结果的基础上，对该类别的其他药物进行了统计分析。使用23种头孢菌素的化学结构来确定40个官能团的存在，并利用已有的蛋白结合数据确定相关关系。有4个官能团与蛋白结合显著相关：四氮唑（正相关）、吡啶鎓、伯胺和季胺（负相关）。在生理pH值下带负电荷的头孢菌素与蛋白结合增加有关。对含四氮唑的头孢菌素和头孢曲松的分析表明，需要进一步研究通过硫亚甲基连接在C3位置的中性或带负电荷的芳香族氮杂环在蛋白结合中的潜在作用。
