- Combination of amino acid/dipeptide with nitric oxide donating oleanolic acid derivatives as PepT1 targeting antitumor prodrugs
-
By taking advantage of the cytotoxic effect of nitric oxide (NO) and PepT1 for molecule-targeted drug delivery, a series of amino acid/dipeptide diester prodrugs of NO-donating oleanolic acid derivatives were designed and synthesized. Two prodrugs 6a and 8a showed potent cytotoxcity, which is probably due to their high PepT1 affinity and NO-releasing ability. Furthermore, the aqueous solubility of the prodrugs was also significantly enhanced because of the hydrophilic amino acid/dipeptide promoiety.
- Fang, Lei,Wang, Meng,Gou, Shaohua,Liu, Xuying,Zhang, Huan,Cao, Feng
-
-
Read Online
- Design and Synthesis of Novel Oleanolic Acid-Linked Disulfide, Thioether, or Selenium Ether Moieties as Potent Cytotoxic Agents
-
A series of novel oleanolic acid (OA)-linked disulfide, thioether, or selenium ether derivatives was synthesized, and their antiproliferative activity was evaluated against human liver cancer (BEL-7402 and HepG-2), colon cancer (HCT116), and normal liver (L02) cell lines using methyl thiazolyl tetrazolium assay (MTT). Preliminary bioassay results revealed that OA derivatives modified at the C3?OH position, i. e., compound a4 containing sulfide ether, exhibited the best antiproliferative activity against BEL-7402 cells, with an IC50 value of 5.70±0.82 μM. Further flow cytometry assays revealed that compound a4 exerted its antiproliferative effects by inducing cell cycle arrest in the G2/M phase leading to apoptosis. Moreover, compared with the lead compound OA and the positive control drug 5-fluorouracil (5-FU), the OA derivatives demonstrated potent antiproliferative activities against the cancer cell lines.
- Li, Ya-Mei,Liu, Chuan-Feng,Luan, Tian,Zhang, Yu
-
-
- Pentacyclic triterpenes. Part 3: Synthesis and biological evaluation of oleanolic acid derivatives as novel inhibitors of glycogen phosphorylase
-
Oleanolic acid and its synthetic derivatives have been identified as novel inhibitors of glycogen phosphorylase. Within this series of compounds, 4 (IC50 = 3.3 μM) is the most potent GPa inhibitor. Preliminary structure-activity relationships of the oleanolic acid derivatives are discussed.
- Chen, Jun,Liu, Jun,Zhang, Luyong,Wu, Guanzhong,Hua, Weiyi,Wu, Xiaoming,Sun, Hongbin
-
p. 2915 - 2919
(2007/10/03)
-