RÉSUMÉ
Objective To synthesize the natural cyclopeptide auyuittuqamide A by Fmoc-based solid phase linear synthesis and liquid phase cyclization. Methods Using 2-chlorotriphenylmethyl chloride (CTC) resin as the solid support, 1,3-diisopropylcarbodiimide (DIC) and 1-hydroxybenzotriazole (HOBt) as the condensing agents, 9-fluorenylmethoxycarbonyl (Fmoc) to protect amino acids were assembled in sequence, and then the linear peptide bearing the protected groups was obtained in presence of trifluoroethanol (TFE) cutting reagent. The protected linear peptide was cyclized with the aid of benzotriazole hexafluorophosphate (PyBOP) and 1-hydroxybenzotriazole (HOBt) in dichloromethane (DCM) solution, followed by trifluoroacetic acid (TFA) deprotection to obtain the cyclic peptide, auyuittuqamide A that was purified by preparative HPLC and characterized by HR-MS and 500MHz 1H-NMR. Results The purity of auyuittuqamide A was more than 95% and the total yield was 5.48%. Conclusion This method has simple synthesis steps and high yield. It is the first to establish a fully synthesis method for the natural cyclic peptide auyuittuqamide A, which lays the foundation for further research of auyuittuqamide A.
RÉSUMÉ
OBJECTIVE: To preliminarily evaluate the targeting and anti-lung cancer effect in vivo in nude mice induced by Cyclo (RGD) and R8 peptides modified ergosterol combined cisplatin liposomes. METHODS: The first step, injected RGD cyclo peptide and R8 peptide-modified, single modified or no modified ergosterol combined cisplatin liposome in the caudal vein of nude mouse bearing the tumor, the body distribution and targeting of each group under the different time points through small animals living imager were observed. The second step, continuously, dose every other day for 14 d, observating the weight of mice and the tumor growth situation. The animals were drawed blood and then were put to death, removing the tumor, the spleen and the lung tissue of all the mice. As the index of the tumor weight, the tumor suppression effect, the level of TGF-β1, TIMPs and TNF-α in serum, the spleen index and changes of the tumor and lung tissue, investigate the tumor suppression effect in mice of the liposomes preliminary. RESULTS: The targeting result of tumor-bearing nude mice displays that the fluorescence intensity of RGD and R8 peptides-modified liposome is the highest and the targeting is most obvious under high concentration and other group of liposome are weaker. Preliminary pharmacodynamics results show that each dosage group of mice have no obvious change in body weight and the high and middle dose group of RGD and R8 peptides-modified liposomes has tumor suppression effect obviously. The high dose group of RGD and R8 peptides-modified liposome is the most significant. It has high expression of cytokines (TNF-α) in serum. The spleen index of middle and low dose group of RGD and R8 peptides-modified liposomes significantly increased compared with positive medicine group. CONCLUSION: RGD cyclo peptide and R8 peptide-modified ergosterol combined cisplatin targeting liposome drug delivery system further improves the tumor targeting and anti-lung cancer effect in vivo.
RÉSUMÉ
The genus of Ziziphus, the most economic genus in the family of Rhamnaceae, contains about 170 species. So far, more than 200 kinds of compounds including triterpenoids, alkaloids, flavonoids, nucleosides, sacharides and other chemical ingredients have been characterized or isolated from the plants of Ziziphus. Among them, triterpenoids mainly nclude the free pentacyclic trit-erpenes and the triterpenoid saponins with the the dammarane-type aglycone; for the flavonoids, besides the O-glycosides constituents, C-glycosides constituents with C-6 or C-8 position replaced by sacharides moiety were also found; alkaloids could be further divided as cyclic peptide alkaloids and soquinoline alkaloids. In this paper, the chemical constituents found n Ziziphus in recent years are summarized, in order to provide reference for their development and utilization.