第12章合成抗菌药和抗病毒药new.ppt

第十二章合成抗菌药和抗病毒药 Chapter 12 Synthetic anti-bacterial agents and anti-virus agents Main Contents Section I Synthetic Anti-bacterial agents 合成抗菌药 磺胺类抗菌药和抗菌增效剂: 代表药物：磺胺甲噁唑,甲氧苄啶;(P223) 喹诺酮类抗菌药: 代表药物：诺氟沙星, 左氟沙星(P229) Section II 抗结核药 合成抗结核药: 代表药物：异烟肼、盐酸乙胺丁醇; 抗结核抗生素: 代表药：利福平。 Section III Synthetic Anti-fungus agents 合成抗真菌药 唑类抗真菌药: 代表药物 ：氟康唑; 非唑类抗真菌药: 代表药：特比萘芬。 Section IV Anti-fugus agents 抗真菌药物 Antimicrobial agents Defination: Antimicrobial agents are the drugs which could inhibit or kill the pathogenic microorganism. 一、磺胺类药物及抗菌增效剂 Sulfonamides also called as sulfa drugs; 1908, German Chemist, Sulfanilamide used as intermediate of azo-dye; 1932, Domagk discover Prontosil, 1933, Foerster used prontosil to treat blood poisoning; To overcome the poor solubility, Prontosil soluble was synthesized for better effect. History of Sulfonamides Development of Sulfonamides 30s in 20 century Rapid 20 kinds clinical drugs; After 40s, Because of the antibiotics such as pennicillin，the importance of sulfa drugs decreased; Sulfa drugs still have lots of merits, such as wide spectra of anti-bacteria, good effects, being took orally, adsorbed rapidly, etc.; Together with TMP, Sulfa drugs are commonly used antibacterial agents; Diuretics and hypoglycemics. Sulfa drugs widely used in clinical 磺胺醋酰 (Sulfaacetamide); 磺胺噻唑 (Sulfathiazole); 磺胺甲氧嗪 (Sulfamethoxypyridazine); 磺胺乙基胞嘧啶 (Sulfa-1-ethyl-cytosine); 柳氮磺胺吡啶 (Salazosulfapyridine). 磺胺类药物的基本结构 Structural features of sulfa drugs: （一）磺胺类药物作用机制 Many theories for mechanism of sulfa drugs: Wood-Fields “Anti-metabolism Theory” 磺胺类药物作用机制的阐明， 确立了抗代谢学说， 为发展新药开辟了一条新途径。 Provide a new method for new drug research. Anti-metabolism Theory 磺胺药与对氨基苯甲酸(PABA)产生竞争性拮抗; PABA(p-Amino Benzoic Acid)为细菌生长所必需; 干扰了细菌的酶系统对PABA利用; 影响细菌生长，产生抑菌活性。 The biological activity of PABA PABA是叶酸的组成部分，叶酸为微生物生长必要物质，也是构成体内叶酸辅酶的基本原料。 PABA在二氢叶酸合成酶的催化下，合成二氢叶酸。 二氢叶酸在二氢叶酸还原酶的作用下还原成四氢叶酸；为细菌合成核酸提供叶酸辅酶。 Contrast between PABA and Sulfonamides Mechanism of Sulfonamides Mechanism