Synthesis And Characteration Of Antitumor Drug Porphyrin-Hydroxycamptothecin Dimer

10-hydroxycamptothecin(HCPT) with clearly anticancer mechanism hasshown wide antitumor activity. However, HCPT has poor cancer-targetingproperties and low accumulation concentration in cancer tissues. Consequently, thehigh dispersion concentration of HCPT in normal tissues would lead to enhancingside effect on normal tissues and reducing its anticancer efficacy. Porphyrin hasbeen applied in the photodynamic therapy of the tumor for decades, the maindrawbacks of porphyrin photosensitizers are poorly soluble in water and thephototoxity of the normal tissues. Therefore, at present, the study on porphyrinphotosensitizer has focused on three aspects: how to increase their solubility inwater, reduce their skin photosensitivity and enhance their anticancer activity.In this paper, a dimer of porphyrin and HCPT was designed and synthesizedby using covalent bond, which may play a synergistic effect in cancer threapy. Onthe one hand, HCPT covalent bonding to porphyrin could increase the solubility ofporphyrin in weak alkaline water. This could greatly reduce the amount of organicsolvent during the course of cancer therapy and effectively aviod the damage onnormal tissues caused by the solvent toxicity, which is benifitial to the clinicalapplication of porphyrin photosensitizers. On the other hand, the affinity ofporphyrin molecule on cancer tissues could enhance the accumulationconcentration of HCPT in cancer tissues, or else, the dispersion concentration ofHCPT in normal tissues decrease. Thus the toxicity of HCPT on normal tissuesmay be reduced and the drug efficacy may be increased. When the dimer wasapplied in tumor therapy and light irradiated, the dimer may attain better treatmenteffect than that of any of porphyrin and HCPT.The specific research progress as follows:1.THPP have been synthesized according to Alder-Longo method. After then,TCLPP was synthesized using chloroacetyl chloride and tetrahydroxyphenyl-porphyrin(THPP). The synthesical method and separation conditions of TCLPP isoptimized by a systematic study on reaction and separation conditions. The finalyield of TCLPP is43%. The structure of two compounds were characterized byUV-Vis spectra, IR spectra, mass spectra and1H NMR and the fluorescenceproperties of two porphyrins have also been investigated. I also study isomerizedproperties of TCLPP, deducing the probable mechanism and structure of theisomer by the alteration of the solubility and IR spectra.2.Two different synthetic routes were taken to synthesize the final compound THPP-HCPT dimer. Duing the experemental processing, the firstsynthetic method was failed to attain the final dimer. After then, the final dimerwas attained by the second route. The synthesical method and separationconditions of dimer is optimized by a systematic study on reaction and separationconditions. The final yield of dimer is10%. The structure of dimer wascharacterized by UV-Vis spectra, IR spectra and mass spectra. The main by-products during the reaction were also analysed and attained reliable conclusion.