大学化学 >> 2025, Vol. 40 >> Issue (3): 42-51.doi: 10.12461/PKU.DXHX202403104

所属专题： 理论与计算化学在化学及其交叉学科教学中的应用

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“头孢配酒”临床悲剧案例的分子机制新解析

周志, 练玉峨, 李雨晴, 高辉, 易伟   

  1. 广州医科大学药学院, 广州 511436
  • 收稿日期:2024-03-29 录用日期:2024-07-04 发布日期:2025-03-19
  • 通讯作者: 高辉, 易伟 E-mail:gaoh9@gzhmu.edu.cn;yiwei@gzhmu.edu.cn
  • 基金资助:
    广东省研究生教育创新计划项目-研究生示范课程建设项目(2021SFKC070)；2023年广医大一流专业建设项目-教学改革研究项目；2022年广东省本科高校教学质量与教学改革工程建设项目(粤教高函【2023】4号)

New Insights into the Molecular Mechanism Behind Clinical Tragedies of “Cephalosporin with Alcohol”

Zhi Zhou, Yu-E Lian, Yuqing Li, Hui Gao, Wei Yi   

  1. School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China
  • Received:2024-03-29 Accepted:2024-07-04 Published:2025-03-19
  • Contact: Hui Gao, Wei Yi E-mail:gaoh9@gzhmu.edu.cn;yiwei@gzhmu.edu.cn

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摘要： “头孢配酒”引发的临床悲剧屡有报道、层出不穷，其原因常被解释为头孢菌素类抗生素药物中含有的甲硫四氮唑或甲硫三嗪侧链抑制了乙醛脱氢酶，从而使得乙醛蓄积中毒(双硫仑样反应)。但最近的多项临床案例显示即便不含甲硫四氮唑或甲硫三嗪的头孢药物，如头孢他啶等也可导致乙醛蓄积中毒，这些现象无法用已有的传统机制合理解释，可能蕴含着新的机制有待阐明。笔者授课时启发同学们将所学计算模拟工具应用于揭示生活化学现象，比如“头孢配酒”现象案例。本文通过分子对接、分子动力学模拟和分子力学泊松-玻尔兹曼表面积(MMPBSA)分别探究头孢哌酮、头孢曲松和头孢他啶与乙醛脱氢酶(ALDH2)的结合模式，进而揭示头孢菌素类抗生素与ALDH2作用新机制。本教学案例不仅为“头孢配酒，说走就走”网络流行语提供更全面更有深度的科学新解释(新科普)，有助于激发大学生关注探寻日常生活中化学现象背后的科学内涵，更重要是的为“头孢配酒”引发临床悲剧案例现象在分子层面的机制创新提供新颖启示和理论依据。

关键词: 头孢菌素类抗生素, 乙醛脱氢酶2, 分子对接, 分子动力学模拟, 生活化学

Abstract: The combination of cephalosporins and alcohol, commonly known as “taking cephalosporin with alcohol”, has frequently led to clinical tragedies. Traditionally, this is attributed to the inhibition of aldehyde dehydrogenase 2 (ALDH2) by the methylthiotetrazole or methyltriazine side chains present in certain cephalosporin antibiotics, resulting in acetaldehyde accumulation and toxicity (disulfiram-like reaction). However, recent clinical cases show that evencephalosporins lacking these side chains, such as ceftazidime, can cause acetaldehyde accumulation, suggesting a potential new mechanism that the existing explanation does not cover. During the lecture, the authors inspired students to apply computational simulation tools to explore everyday chemical phenomena, such as the “cephalosporin with alcohol” scenario. This study uses molecular docking, molecular dynamics simulation, and molecular mechanics Poisson-Boltzmann surface area (MMPBSA) calculations to investigate binding modes of cephoperazone, ceftriaxone, and ceftazidime with ALDH2, uncovering a new mechanism of interaction between cephalosporins and ALDH2. This case study not only provides a deeper scientific explanation of the popular online phrase "taking cephalosporin with alcohol is danger to health" but also encourages students to explore the scientific basis of everyday chemical phenomena. More importantly, it offers novel insights and theoretical evidence for the molecular mechanisms underlying clinical tragedies caused by cephalosporin-alcohol interactions.

Key words: Cephalosporin antibiotics, Aldehyde dehydrogenase 2, Molecular docking, Molecular dynamics simulation, Life chemistry