title: Synthesis of acyl oleanolic acid-uracil conjugates and their anti-tumor activity.
abstract: BACKGROUND
  Oleanolic acid, which can be isolated from many foods and medicinal plants, has been reported to possess diverse biological activities. It has been found that the acylation of the hydroxyl groups of the A-ring in the triterpene skeleton of oleanolic acid could be favorable for biological activities. The pyrimidinyl group has been constructed in many new compounds in various anti-tumor studies.
  
  
  RESULTS
  Five acyl oleanolic acid-uracil conjugates were synthesized. Most of the IC50values of these conjugates were lower than 10.0 μM, and some of them were even under 0.1 μM. Cytotoxicity selectivity detection revealed that conjugate4cexhibited low cytotoxicity towards the normal human liver cell line HL-7702. Further studies revealed that4cclearly possessed apoptosis inducing effects, could arrest the Hep-G2 cell line in the G1 phase, induce late-stage apoptosis, and activate effector caspase-3/9 to trigger apoptosis.
  
  
  CONCLUSIONS
  Conjugates of five different acyl OA derivatives with uracil were synthesized and identified as possessing high selectivity toward tumor cell lines. These conjugates could induce apoptosis in Hep-G2 cells by triggering caspase-3/9 activity.Graphical abstractFive acyl oleanolic aicd-uracil conjugates were synthesized. These conjugates exhibited selective cytotoxicity toward tumor cells achieved via inducing apoptosis by activation of caspase-3/9.
authors.affiliation: State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin, 541004 People's Republic of China ; Biochemistry and Pharmacology of Sport School, Guangxi Normal University, Guilin, 541004 People's Republic of China.
authors.forename: Wei-Bin
authors.initials: WB
authors.lastname: Mo
authors.affiliation: State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin, 541004 People's Republic of China ; School of Chemistry and Pharmacy, Guangxi Normal University, Guilin, 541004 People's Republic of China.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Su
authors.affiliation: State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin, 541004 People's Republic of China ; School of Chemistry and Pharmacy, Guangxi Normal University, Guilin, 541004 People's Republic of China.
authors.forename: Jia-Yan
authors.initials: JY
authors.lastname: Huang
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009 People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin, 541004 People's Republic of China ; School of Chemistry and Pharmacy, Guangxi Normal University, Guilin, 541004 People's Republic of China.
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Chen
authors.affiliation: State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin, 541004 People's Republic of China ; School of Chemistry and Pharmacy, Guangxi Normal University, Guilin, 541004 People's Republic of China.
authors.forename: Ke-Guang
authors.initials: KG
authors.lastname: Cheng
keywords: Acyl oleanolic acid; Anti-tumor activity; Apoptosis; Cytotoxicity; Uracil