In silico ADME and Toxicity Prediction of Ceftazidime and Its Impurities

Conclusion Pyridine itself may be not toxic, but the N atom on the pyridine ring links with methyl to form a quaternary amine group that becomes the toxic C-3 substituent of CAZ. In addition, the E-isomer is important in CAZ quality. The formation of CAZ E-isomer is related to light and other factors. Therefore, the stability of CAZ E-isomer is critical. Impurity D may be especially neurotoxic and genotoxic. Impurity I may have hepatotoxicity. They are the key contaminant to control. In summary, the main toxic functional groups of CAZ and its impurities are the β-lactam ring of the scaffold, the quaternary amine group of the C-3 side chain, and the acetic acid (salt) on the C-7 side chain. This information provides a theoretical and experimental basis for predicting the toxicity of cephalosporins and their impurities, and for the quality control of these impurities. Author Contributions JZ and CH conceived, designed, and supervised the study. YH performed the ADMET prediction and docking experiments and analyzed the data. YH and CH wrote the manuscript. XZ performed the molecular conformation analysis. BM and PZ performed the ADMET prediction. Funding This work was supported by National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2017ZX09101001-007), and Development Research Foundation for Young Scientists of National Institutes for Food and Drug Control (2017A1). Conflict of Interest Statement The au...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research