Synthesis and Anti-tumor Activity of New Rotundic Acid Derivatives / 中国实验方剂学杂志

Objective:To design and synthesize series of rotundic acid derivatives by introducing aromatic ester groups with rotundic acid as the parent nucleus, test their anti-tumor activity in vitro,investigate the structure-activity relationship of rotundic acid derivatives in inhibiting tumor cell proliferation, and obtain the novel rotundic acid derivatives with high anti-tumor activity. Method:Compounds 1-8 were synthesized with rotundic acid as the initial raw material through the 28-etherification,3β and 23di-aromatic esterification eaction. The anti-tumor activities in vitro were evaluated by MTT assay against A375 (human malignant melanoma cells),HeLa (human cervical cancer cells),SPC-A1 (human lung adenocarcinoma cells),and HepG2 (human liver cancer cells). Result:Compounds 2-8 were new compounds. Their structures were identified by melting point (MP),high resolution electrospray ionization tandem mass spectrometry (HR-ESI-MS),1H nuclear magnetic resonance (1H-NMR) and 13 C nuclear magnetic resonance (13 C-NMR). MTT results showed that compounds 3,5 and 8 exhibited significant anti-tumor activity, especially compound 5 was found to have the best inhibition activity on HeLa,A375, HepG2 and SPC-A1 with IC50 values of (5.25±1.08),(5.99±0.88),(3.31±1.89),(5.74±1.78) μmol·L-1, 1.92,3.22,3.79, 3.72 times of that of rotundic acid,respectively. Conclusion:Compound 5 has significant anti-tumor activity with great significance for further research and development of new anti-tumor medicines.

Synthesis of Echinocystic Acid Derivatives and Inhibitory Effect on Lipase / 中国实验方剂学杂志

Objective:Echinocystic acid(EA)is a kind of oleanolic pentacyclic triterpenoid compound,due to its main structural features of stability and less active sites,the structures of EA were modified in this paper to synthesize a series of EA derivatives, improve their bioavailability, and investigate their inhibitory effect on lipase. Method:In this study,EA derivatives were designed and synthesized from EA,which is a natural lipase inhibitor. Their inhibitory effects on lipase were tested by using 2,4-dinitrophenyl butanoate(PNPB) method. Result:Nine compounds were synthesized,and their structures were characterized by infrared spectrum (IR), ultraviolet spectrum (UV), mass spectrum (MS), nuclear magnetic resonance spectrum (1H-NMR and 13 C-NMR),all of which were identified as new compounds. Further experiments on the inhibitory effect on lipase showed that compounds 1-9 had higher inhibitory effects than EA,IC50=7.03,2.05,2.14,3.65,3.24,0.28,0.34,0.46,and 0.39 g·L-1. Compounds 6-9 had higher inhibitory effect than Orlistat(IC50=0.53 g·L-1). Inhibition rates were as follows:6 > 7 > 9 > 8 > Orlistat> 2 > 3 > 5 > 4 > 1 >EA. Conclusion:It is feasible to design and synthesize derivatives with EA as the lead compound to improve the inhibitory effect on lipase.