抗生素的作用机制.ppt

Chapter 11 Antibiotics 抗生素的作用机制 Mechanism of antibiotic 1.干扰细菌细胞壁合成 2. 损伤细菌细胞膜 3. 抑制细菌蛋白质合成 4. 抑制细菌核酸合成 5. 增强吞噬细胞的功能 1. To interfere with the synthesis of bacterial cell wall 2. To damage the cell membrane of bacteria 3. To inhibit protein synthesis of bacteria 4. To inhibit nucleic acid synthesis of bacteria 5. To enhance the function of phagocytes To be classified according to chemical structure： 1，β-内酰胺类,β-lactams 2，四环类, tetracycline antibiotics 3，氨基糖苷类, Aminoglycoside antibiotics 4，大环内酯类, Macrolide antibiotics 5，其他类, other types The basic structure ofβ-lactam antibiotics The characteristics of the chemical structure ①β-lactam ring: 四元β-内酰胺环环通过N原子和邻近的第三碳原子与另一个五元环或六元环相稠合，青霉素的稠合环是氢化噻唑环，头孢菌素是氢化噻嗪环。 ②A carboxyl group: 与β-内酰胺环稠合的环上都有一个羧基。 ③An amide side-chain: 内酰胺环羰基α-为碳都有一个酰胺基侧链。 ④Stereochemistry: β-内酰胺环为一个平面结构。但两个稠合环不共平面，青霉素沿N1-C5轴折叠，头孢菌素沿N1-C6轴折叠. ⑤Polarimitry structure: 青霉素类抗生素的母核上有3个手性碳原子，8个旋光异构体中只有绝对构型为2S，5R，6R具有活性。头孢菌素类抗生素的母核上有2手性碳，4个旋光异构体，绝对构型是6R，7R。β-内酰胺类抗菌活性不仅与母核的构型有关。而且还与酰胺基上取代基的手性碳原子有关，旋光异构体间的活性有很大的差异。 The mechanism of β-lactam antibiotics Resistance and mechanism of -lactam antibiotics Benzylpenicillin Alkaline conditions: Prodrugs of penicillin Semi-synthetic penicillin Shortcomings of Penicillin : non acid- resistent, non enzyme-resistent, narrow anti-bacterial spectrum and allergic reactions Semi-synthetic penicillins: Acid-resistant penicillin Enzyme-resistant penicillin Broad-spectrum penicillin Compounds of Penicillin and β-lactamase inhibitor Acid-resistant penicillin 天然青霉素中青霉素V可以口服，不易被胃酸破坏,说明具有耐酸性质，虽其抗菌活性低于青霉素G,但其耐酸的性质值得注视。它的结构与青霉素G的差别是6位酰胺基上是苯氧甲基，为吸电子基团，可降低羟基上的电子密度，从而阻止了侧链羰基电子向β-内酰胺环的转移，增加了对酸的稳定性，根据同系物原理设计合成了在酰胺基α位引入O、N、X等电负性原子的衍生物。 Enzyme-resistant Penicillin Oxacillin Series Broad-spectrum penicillin Chemical stability The structure-activity relationships of penicillins The side-chain at 6 is important to the antimicrobial spectrum. To change its polarity, make it go through cell membrane easily can expand its antibacter