Synthesis And Antitumor Activity Of Protoporphyrin And Tryptamine Derivatives

Porphyrins are an important class of macrocyclic conjugated aromatic heterocyclic compounds,which not only have photosensitivity,but also can control the proliferation of different cancer cells to a certain extent.Therefore,it is often used in the construction and research of anticancer drug carrier.Protoporphyrin has attracted much attention because of its high biocompatibility and inhibitory effects on cancer cells.In the thesis,a series of protoporphyrin derivatives were synthesized by introducing active groups into the two carboxyl functional groups of protoporphyrin through the amide reaction,and the structure of the synthesized compounds was characterized and determined by NMR（nuclear magnetic resonance spectroscopy）and MS（Mass Spectrometry）,and the antitumor activity of the synthesized protoporphyrin derivatives was detected by MTT method.Tryptamine is an important natural chemical,it can promote a variety of natural alkaloid synthesis,often used in biology and medicine and other fields.In recent years,the research of small molecule tryptamines anticancer drugs has attracted much attention.In this paper,5-methoxytryptamine,the active group in melatonin,was selected and modified by functional groups to synthesize a series of tryptamine derivatives.The structure of the synthesized compounds was identified through corresponding detection,and the anti-tumor activity of the synthesized tryptamine derivatives was detected by MTT method.The conclusion of this paper is as follows:1.Protoporphyrin was prepared by direct demetallization of heme,followed by the preparation of five protoporphyrin derivatives which were synthesized by amide reaction using protoporphyrin as the raw material.Cytotoxicity tests were performed human breast cancer cells（MCF-7）,human colon cancer cells（HCT 116）,human glioma（U251）,and human lung cancer cells（A549）.According to the test results,compounds A2 and A4 have the potential to be precursors in the field of antitumor drug research.Compounds A4 on human brain tumor inhibitory effect(IC₅₀=0.58μM)is very close to the clinical drug of Bortezomib which is a boron substituted drug in the market.The promising data provided a good base for the future research.2.Study on the synthesis of tryptamine derivatives and their inhibitory activities on cancer cells were accomplished using 5-methoxytryptamine as the matrix.22tryptamine derivatives were synthesized by amide reaction using cinnamic acid derivatives,benzoic acid and phenylacetic acid derivatives as raw materials.Cytotoxic activities of the synthesized compounds were tested on corresponding cancer cells including MCF-7,U251,HCT 116,A375 and A549 cells.Cytotoxic activity of the synthesized compounds was tested on human breast cancer cells（MCF-7）,human glioma（U251）,human colon cancer cells（HCT 116）,human lung cancer cells（A549）and melanoma cancer cells（A375）.The results showed that cytotoxicities of four products,B3,B4,B5 and B7,synthesized from 5-methoxytryptamine and cinnamic acid derivatives,against cancer cells were all excellent.All of these compounds are valuable for further study and may provide precursor compounds for further research on small-molecule antitumor drugs.