Association (micellization) and partitioning of aglycon triterpenoids.
Micellization and solution properties of the aglycon triterpenoids asiatic acid (AA) and madecassic acid (MA) were examined experimentally and in computational simulations. AA and MA belong to the large class of bioactive aglycon triterpenoids, for which limited physicochemical data are available. In this study, solubility, partition coefficient, critical micelle concentrations (CMC), and surface tensions of AA and MA were measured. Reverse phase HPLC data, supported by dye probe experiments and drop shape analysis, showed the CMC in phosphate buffered saline (PBS) to be 15+/-2 microM, and 86+/-9 microM for AA and MA, respectively. The surface tensions of AA and MA in PBS were 64.1 and 64.4 mN/m, respectively. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry indicated the aggregation numbers of AA and MA to be 5 to 7. Molecular dynamics simulations confirmed that molecular association could occur between 5 and 7 molecules in solution. The IC(50) of AA and MA on human small cell carcinoma and human glioblastoma cell lines was 25+/-5 microM and 66+/-13 microM, respectively. The IC(50) is within the range of calculated CMC of AA and MA in bioassay media, suggesting that the micellar aggregates may lead to their cytotoxicity.
Biomaterials Science and Engineering Laboratory, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139, USA.
Marjan
M
Rafat
Kit Wah
KW
Fong
Arthur
A
Goldsipe
Brian C
BC
Stephenson
Samuel T
ST
Coradetti
T G
TG
Sambandan
Anthony J
AJ
Sinskey
Chokyun
C
Rha
D001681:Biological Assay; D018288:Carcinoma, Small Cell / Q000188:drug therapy; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D005909:Glioblastoma / Q000188:drug therapy; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy; D008823:Micelles; D008968:Molecular Conformation; D053978:Pentacyclic Triterpenes; D012995:Solubility; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013500:Surface Tension; D014315:Triterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
D008823:Micelles; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C017032:asiatic acid; C001669:madecassic acid