Preparation, Solubilization and In vitro Anti-tumour Effect of Water-soluble Betulinic Acid/Oligo(polylvinylamino) Bridged bis(β-cyclodextrin)s Complexes
Yiou Tao
Department of Chemistry, College of Science, Northeast Forestry University, Harbin 150040, P. R. China
Yang Han
Department of Chemistry, College of Science, Northeast Forestry University, Harbin 150040, P. R. China
Shihui Dong
Department of Chemistry, College of Science, Northeast Forestry University, Harbin 150040, P. R. China
Xiaocheng Fan *
Department of Chemistry, College of Science, Northeast Forestry University, Harbin 150040, P. R. China
Ting Wang
Department of Chemistry, College of Science, Northeast Forestry University, Harbin 150040, P. R. China
Xiufeng Yan
Alkali Soil Natural Environmental Science Center, Northeast Forestry University, Key Laboratory of Saline-Alkali Vegetation Ecology Restoration in Oil Field, Ministry of Education, Harbin 150040, P. R. China
*Author to whom correspondence should be addressed.
Abstract
A series of water-soluble betulinic acid complexes of betulinic acid/oligo(diethylenetriamino) bridged bis(β-cyclodextrin) (BA/DT-β-CD), betulinic acid/oligo(triethylenetetramino) bridged bis(β-cyclodextrin) (BA/TT-β-CD) and betulinic acid/oligo(tetraethylenepentamino) bridged bis(β-cyclodextrin) (BA/TP-β-CD) were prepared and characterized. IR, SEM, MS and 1H NMR were used to characterise these complexes. The results show that the two cyclodextrin cavities and tether groups of the aforementioned bis(β-cyclodextrin)s can form a well-organized pseudo cavity to accommodate the branch group of BA, respectively. By UPLC analysis, the water solubility was remarkably increased to approximately 310.97, 144.94 and 75.04 μg mL-1 by the solubilising effects of DT-β-CD, TT-β-CD and TP-β-CD, respectively. Furthermore, the anti-tumour effect against HeLa cell line was tested by MTT assay, and the IC50 values of BA in BA/DT-β-CD complex water solutions are 103.89 ± 5.12 μmol L-1, which possess an obvious antiproliferative activity against HeLa cell line.
Keywords: Betulinic acid, Bis(β-cyclodextrin), Oligo(polylvinylamino) bridged, water solubility, anti-tumor