title: A 3D-QSAR Study on Betulinic Acid Derivatives as Anti-Tumor Agents and the Synthesis of Novel Derivatives for Modeling Validation.
abstract: BACKGROUND
  Betulinic acid is a lupane-type triterpene firstly extracted from the bark of white birch. It has displayed anti-inflammatory, antioxidant, anti-HIV and selective cytotoxicity.
  
  
  OBJECTIVE
  To understand the structure- anti-tumor activity relationship of betulinic acid and betulin derivatives and to synthesize novel anti-tumor derivatives of betulinic acid and betulin.
  
  
  METHODS
  The 3D-QSAR methods including CoMFA and CoMSIA methods were performed to study the structureanti- tumor activity relationship of betulinic acid (BA) and betulin (BE) derivatives.
  
  
  RESULTS
  According to the models, near the C-3 site, non-bulky, negatively charged electron-donating, hydrophobic, non-hydrogen-bond-donating and hydrogen-bond-accepting groups are favored to the activity. Around the C-28 site, the bulky, positively charged electron-withdrawing and hydrophobic groups are favored, whereas hydrophilic groups may be introduced at the terminal of the side chain. Based on the models, BA and BE were esterified with substituted amino acid derivatives achieving novel derivatives for the modeling validation.
  
  
  CONCLUSIONS
  The experimental results verified the modeling rules, and showed when different rules may apply to the new structures, the steric effects might be more important. The synthesized derivatives were showed promising cytotoxicity against tested cancer cell lines.
authors.affiliation: School of Chemical and Environmental Engineering, Harbin University of Science and Technology, Harbin, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Ding
authors.affiliation: Alkali Soil Natural Environmental Science Center, Northeast Forestry University; Key Laboratory of Saline-alkali Vegetation Ecology Restoration in Oil Field, Ministry of Education, Harbin, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Alkali Soil Natural Environmental Science Center, Northeast Forestry University; Key Laboratory of Saline-alkali Vegetation Ecology Restoration in Oil Field, Ministry of Education, Harbin, China.
authors.forename: Meixuan
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Alkali Soil Natural Environmental Science Center, Northeast Forestry University; Key Laboratory of Saline-alkali Vegetation Ecology Restoration in Oil Field, Ministry of Education, Harbin, China.
authors.forename: Shaoming
authors.initials: S
authors.lastname: Wang
authors.affiliation: Alkali Soil Natural Environmental Science Center, Northeast Forestry University; Key Laboratory of Saline-alkali Vegetation Ecology Restoration in Oil Field, Ministry of Education, Harbin, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Alkali Soil Natural Environmental Science Center, Northeast Forestry University; Key Laboratory of Saline-alkali Vegetation Ecology Restoration in Oil Field, Ministry of Education, Harbin, China.
authors.forename: Haijing
authors.initials: H
authors.lastname: Qu
authors.affiliation: Alkali Soil Natural Environmental Science Center, Northeast Forestry University; Key Laboratory of Saline-alkali Vegetation Ecology Restoration in Oil Field, Ministry of Education, Harbin, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.affiliation: Alkali Soil Natural Environmental Science Center, Northeast Forestry University, Harbin, China; Key Laboratory of Saline-alkali Vegetation Ecology Restoration in Oil Field, Ministry of Education, Harbin, China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Yan
authors.affiliation: Alkali Soil Natural Environmental Science Center, Northeast Forestry University, Harbin, China; Key Laboratory of Saline-alkali Vegetation Ecology Restoration in Oil Field, Ministry of Education, Harbin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D053978:Pentacyclic Triterpenes; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000094062:Betulinic Acid
chemical_list: D000970:Antineoplastic Agents; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D000094062:Betulinic Acid
keywords: 3D-QSAR; Betulinic acid; CoMFA; CoMSIA; betulin; modeling validation