The Study Of Hydrophilic Amino Acid And Oligopeptides Modified β-elemene

β-Elemene is the mainly active anticancer component in Chinese medicinecurcuma wenyujin, has the "double effect" of antitumor and immune regulation,which has a better prospect in clinical use. However, β-elemene composed of onlycarbon and hydrogen, is fat-soluble drug with poor water solubility, which restrictsits biological activity and limits cancer therapy efficacy.In this thesis, we made use of the good biocompatibility and strong water-solublelysine, proline, glycine and the oligopeptides to explore the modification of β-elemenestructure. It exploited the best bit of allyl selective chlorination to first synthesizeβ-elemene single chloride, and then lysine and proline were introduced in theβ-elemene matrix structure through the dear bimolecular nucleophilic substitutionreaction (SN2reaction).On the basis of the method of solid phase synthesis peptide,the synthetics were connected to the second amino acids to receive β-elemeneoligopeptides derivatives. The structure of the synthetics were characterized byIR,1HNMR, MS. Based on the solubility standard of the2010“ChinesePharmacopoeia” second, the solubility of target products were tested in purified waterat25℃. The results showed that the solubility of N-(elemene-13-yl) Proline was56.5mg/mL, the solubility of N-(elemene-13-yl)Lysine was25.8mg/mL, the solubility ofN-(elemene-13-yl)-Lysine-Lysine was123mg/mL,N-(elemene-13-yl)-Lysine-Prolinewas157mg/mL, N-(elemene-13-yl)-Lysine-Glycine was107mg/mL. All the targetcompounds were more solubler than that of β-elemene. We selected of human lungcancer (A549), human cervical carcinoma cell (HeLa),gastric cancer cell line (SGC-7901) and human glioma cells (U251) to test anticancer activity in vitro, andthe inhibitory effects of target compounds on proliferation of cancer cells weremeasured by MTT assay. N-(elemene-13-yl) Proline showed inhibition against A549cells and its IC50was0.196μmol/mL; N-(elemene-13-yl)Lysine showed inhibitionagainst HeLa,SGC-7901cells and the IC50were0.118μmol/mL,0.135μmol/mL;N-(elemene-13-yl)-Lysine-Lysine showed inhibition against HeLa,U251cells and the IC50were0.379μmol/mL,0.235μmol/mL. The results revealed that the amino acid andoligopeptides derivatives of β-elemene were soluble and potent anti-tumor agents,which had the significance of research and value of application.