Amino Acid Derivatives of Ligustrazine-Oleanolic Acid as New Cytotoxic Agents
AbstractA series of novel ligustrazine-oleanolic acid (TOA) derivatives were designed, and synthesized by conjugating amino acids to the 3-hydroxy group of TOA by ester bonds. Their cytotoxicity was evaluated on four cancer cell lines (HepG2, HT-29, Hela and BGC-823) by standard MTT assays. The ClogP values were calculated by means of computer simulation, and logP values of both 3β-glycine ester olean-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methyl ester (6a) and TOA were determined using a shake flask-ultraviolet spectrophotometry method. It was found that 6a and the 3β-L-lysine ester-6g not only displayed good cytotoxicity (IC50 < 3.5 μM) but also possessed better hydrophilicity than TOA. Moreover, 6a (IC50 = 4.884 μM) had lower nephrotoxicity than both 6g (IC50 = 2.310 μM) and cisplatin (CDDP, IC50 = 3.691 μM) on MDCK cells. Combining Giemsa and DAPI staining, it was further verified that 6a could induce HepG2 apoptosis via nuclei fragmentation and had lower nephrotoxicity. In addition, the structure-activity relationships of these derivatives are briefly discussed. View Full-Text
Scifeed alert for new publicationsNever miss any articles matching your research from any publisher
- Get alerts for new papers matching your research
- Find out the new papers from selected authors
- Updated daily for 49'000+ journals and 6000+ publishers
- Define your Scifeed now
Chu, F.; Xu, X.; Li, G.; Gu, S.; Xu, K.; Gong, Y.; Xu, B.; Wang, M.; Zhang, H.; Zhang, Y.; Wang, P.; Lei, H. Amino Acid Derivatives of Ligustrazine-Oleanolic Acid as New Cytotoxic Agents. Molecules 2014, 19, 18215-18231.
Chu F, Xu X, Li G, Gu S, Xu K, Gong Y, Xu B, Wang M, Zhang H, Zhang Y, Wang P, Lei H. Amino Acid Derivatives of Ligustrazine-Oleanolic Acid as New Cytotoxic Agents. Molecules. 2014; 19(11):18215-18231.Chicago/Turabian Style
Chu, Fuhao; Xu, Xin; Li, Guoliang; Gu, Shun; Xu, Kuo; Gong, Yan; Xu, Bing; Wang, Mina; Zhang, Huazheng; Zhang, Yuzhong; Wang, Penglong; Lei, Haimin. 2014. "Amino Acid Derivatives of Ligustrazine-Oleanolic Acid as New Cytotoxic Agents." Molecules 19, no. 11: 18215-18231.