三、Folicacidantimetabolites（叶酸拮抗剂）.pptVIP

5-FdUMP binds to thymidylate synthetase to give an intermediate that resembles the intermediate formed with uridylic acid, however, this intermediate cannot break down and the enzyme is inhibited 胸腺嘧啶脱氧核甙酸合成酶 Metabolism of 5-fluorouracil Synthesis of 5-FU base Ring open product Stability in NaHSO3 （二） Cytarabine （ARA-C,阿糖胞苷） Pyrimidine antimetabolite in which sugar is modified 胞嘧啶衍生物 胞嘧啶 阿拉伯糖 The normal 2’ configuration is α 主要用于治疗急性粒细胞白血病 Metabolic activation and inactivation of ARA-C 阿糖胞苷在体内的代谢激活与失活 Inactive species Mechanism of Action for ARA-C ARA-CTP inhibits the conversion of cytidylic acid to 2’-deoxycytidylic acid ARA-CTP 抑制磷酸胞苷转换为脱氧磷酸胞苷 ARA-CTP also inhibits DNA-dependent DNA polymerase 抑制依赖DNA的DNA多聚酶 ARA-C causes miscoding after being incorporated into DNA 掺入DNA后编码错误，DNA合成终止 Synthesis of Cytarabine D-阿拉伯糖 氰胺 2-氨基-D-阿糖噁唑啉 cyclocytidine 氯代丙烯氰 二、 Purine Antimetabolites （嘌呤拮抗剂） 巯嘌呤 Poor water solubility 主要用于各种急性白血病的治疗 Na2SO3/H2O Na+ 6-MPMP inhibits several key enzymes involved in the biosynthesis of purine The overall action of 6-MP is inhibition of the de novo synthesis of purines Mechanism of Action of 6-mercaptopurine Synthesis of Mercaptopurine 硫脲 三、 Folic acid antimetabolites （叶酸拮抗剂） Folic acid, 叶酸 Folic acid is an essential component for the biosynthesis of DNA and RNA 叶酸是核酸生物合成的关键组分 An important factor for red cell development 是红细胞发育生长的重要因子 Pterine， Pteridoxamine，碟呤 MTX competes with the normal substrate folic acid, inhibits DNA synthesis Folic acid antimetabolites （叶酸拮抗剂） 叶酸 氨基碟呤，白血宁 甲氨碟呤， MTX Other Anticancer Drugs 1. Taxol, or Paclitaxel （紫杉烷） Antimicrotuble Agent Taxol promotes the assembly of microtubules from tubulin dimers Formula：C47H51NO14。MW：853.92， 1971年 Pacific Yew，1967 红豆杉 Ovarian, breast, lung and colon cancer * Cancer Therapy The specific approach used to treat cancer depends upon the specific type, location, and stage of the cancer Fundamental techniques available to treat cancer: Surgery Radiat