chapter 13 antineoplasticdrugs概要1.pptVIP

Classification by mechanism 1. Alkylating agents 2. Antimetabolites 3. Drugs intefering with synthesis of protein of tumor cells 13.1 Biological alkylating agents 1.Nitrogen mustards 2.Ethylene imines 3.Sulfonates and halogenated polyols 4.Nitrosourea Physicochemical properties of cyclophosphamide White crystal or crystalline powder (失去结晶水即液化) Soluable in water, unstable in aqueous solution and easily hydrolyze, easily decompose under heating condition. Cyclophosphamide is a prodrug.在肝脏被活化，经非酶促的β-消除反应生成丙烯醛（膀胱毒性）、磷酰氮芥及去甲氮芥，三者都是较强的烷化剂。 美法仑 Melphalan 氮芥类药物是通过在体内转变成乙撑亚胺中间体发挥烷化剂作用，乙撑亚胺的磷酰胺衍生物，可提高抗肿瘤作用及减小毒性。 Tepa was clinical used for treatment of leukaemi。 Thiotepa changed into tepa in vivo. Clinical for the treatment of breast cancer, ovarian cancer, bladder cancer, and so on. 13.3.2 Topoisomerase Ⅰinhibitors 阿霉素（多柔比星）(doxorubicin) 紫杉醇 taxol 盐酸阿糖胞苷 Cytarabine hydrochloride 1-β-D-呋喃型阿拉伯糖胞嘧啶盐酸盐 1-β-D-arabinofuranosyl cytosine hydrochloride 用于治疗急性粒细胞白血病。 Clinical mainly for the treatment of acute myeloid leukemia. Metabolism and stability: 盐酸阿糖胞苷会迅速被肝脏中的胞嘧啶脱氨酶作用脱氨，生成无活性的尿嘧啶阿糖胞苷，故口服吸收较差，通常是通过静脉连续滴注给药。 Prodrugs of cytarabine: 为了减轻体内的脱氨失活，将其氨基酰化成前药，如依诺他滨、棕榈酰阿糖胞苷，抗肿瘤活性强而持久。 甲氨蝶呤 methotrexate 4-[4[[(2,4-二氨基-6-蝶啶）-甲基]-N-甲胺基]-苯甲酰基]-L-谷氨酸 4 - [4 [[(2,4 - diamino -6 - Pteridinyl) -methyl]-N-methylamino] - benzoyl]-L-glutamaic acid 甲氨蝶呤是叶酸的拮抗剂，对二氢叶酸还原酶的亲和力比二氢叶酸强1000倍，几乎是不可逆地和二氢叶酸还原酶结合，使二氢叶酸不能转化为四氢叶酸，从而影响辅酶F的生成，抑制DNA和RNA的合成。 Methotrexate is an antagonist of folic acid, the affinity to dihydrofolate reductase is 1000 times stronger than dihydrofolate, almost irreversibly combined with dihydrofolate reductase, so that dihydrofolate can not be transformed into tetrahydrofolate, so methotrexate interfere with the generation of coenzyme F, inhibiting the biosynthesis of DNA and RNA of tumor cells. For treatment of acute leukemia, chorion cell carcinoma and malignant mole. 强酸条件下不稳定，酰胺键水解，生成谷氨酸和蝶呤酸而失去活性。 Bleomycin, seperated from streptomyces verticillus. Broken the DNA chains to