第七章抗肿瘤药.pptxVIP

Chapter 13 Antineoplastic Agents;Classification by mechanism; 13.1 Biological alkylating agents; Bioalkylating agents are cytotoxic drugs. In vivo, it is able to form a positive charged carbon-ion or other active electrophilic groups, and then the electrophilic ions combine covalently with electron rich groups (such as amino, sulfhydryl, hydroxyl, carboxyl, phosphate, etc.) of the cells of biological macromolecules (DNA, RNA, enzymes), lead to the breaking of DNA molecule, at last result in the death of tumor. However, bioalkylating drugs also inhibit the normal cells with the property of rapid proliferation such as bone marrow cells, intestinal epithelial cells at same time. So the bioalkylating agents have more serious side effects, such as nausea, vomiting, bone marrow suppression and hair loss. Clinical usually are carrying on combined use with other drugs.;General formula of nitrogen mustards;Mechlorethamine hydrochloride;Different R：脂肪氮芥、芳香氮芥;Alkylation process:; It is usually used as injection drug of aqueous solution, which pH value maintained at 3.0 ~ 5.0.;Nitromin: Reduced the possibility of formation of ethylene imine for the reduced electronic cloud on nitrogen. Nitromin is less toxicity, but also the reduced anti-tumor activity.;2. Aromatic nitrogen mustards: The introduction of aromatic ring led to reduction of alkalescence by reason of conjugation, so mechanism was changed, no formation of cyclic ethylene imine ion but the formation of carbon cation intermediate.;;Cyclophosphamide;Physicochemical properties of cyclophosphamide;;Cyclophosphamide has a broad spectrum of anti-tumor, clinical for treatment of malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, lung cancer etc.;;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.;Sulfonates and h