Synthesis And Biological Evaluation Of Bifunctional Anticancer Drugs

At present, some nitrogen mustard antitumor drugs are used in the clinical, such as cyclophosphamide, ifosfamide, formylmerphalan tablets, they are widely used in clinical, but the lack of targeting, serious side effects and other shortcomings severely limit nitrogen mustard class of drugs widely used. Now the research and development about Nitrogen mustard antitumor compounds are focused on the modified vector, mainly through the design of a targeting carrier of nitrogen mustard drugs to reduce side effects.Cyclophosphamide is a class drug of nitrogen mustard. Cyclophosphamide is inactive on the tumor cells in vitro; but in the body it can be oxidized to4-hydroxy cyclophosphamide by the liver cytochrome P450, and can be further oxidized to nontoxic4-keto-cyclophosphamide, but also tautomerism structure formation of the open loop of aldehyde compounds, aldehyde compounds can be further oxidized to the nontoxic carboxyl compounds can also be non-enzymatic reaction of acrolein, in which the enzymatic reaction to generate non-toxic compounds in normal tissues,in tumor tissue lacks the normal tissue enzymes, cannot be nontoxic conversion of acrolein only by non-enzymatic reaction, phosphoryl nitrogen mustard to play the anti-tumor effect.With the improvement of the medical level, the cancer treatment has also made great progress, the survival of cancer patients was significantly prolonged.the quality of cancer patients life was significant improved, with the development of treatment, the tumor complications,such as infection and pain also increases,which seriously affect the survival time and life’s quality of cancer patients.the treatment of cancer complications tend to lag in clinical, and multiple administer caused great pain to the patient; at the same time, many anticancer drugs at worktherapeutic effect, produces byproducts in the body caused the toxicity of metabolites.Based on the above considerations, the authors designed and synthesized a bifunctional drug, when it play the role of antitumor, either to reduce the side effects of drugs, but also relax and treat tumor complications.This thesis aims to study the synthesis of bifunctional nitrogen mustard anticancer drugs, study the crosslinking activity about newly synthesized bifunctional nitrogen mustard antitumor drugs on plasmid pBR322DNA by alkaline agarose gel electrophoresis, study the toxicity of anticancer drugs to tumor cells by use MTT assay, study the analgesic activity of bifunctional nitrogen mustard antitumor drugs in mice by using the hot plate method.Studies have shown that newly synthesized bifunctional nitrogen mustard antitumor drugs with better biological activity.