Binding and location of dipyridamole derivatives in micelles: the role of drug molecular structure and charge.
Binding and localization of the vasodilator and antitumor drug coactivator dipyridamole (DIP) and of its three derivatives, RA14, RA47 and RA25 (DIPD), to cationic (cetyltrimethylammonium chloride), anionic (sodium dodecylsulfate), zwitterionic (N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate), and neutral (t-octylphenoxypolyethoxyethanol) micelles was studied using fluorescence, optical absorption and 1H NMR spectroscopy. The analysis of NMR, optical absorption and fluorescence data indicates that the depth of localization of the drugs in the micelles from the surface decreased in the order DIP > RA14 > RA47 > RA25. The binding constants for the neutral drug forms change in the same order in the range of 1400-3100 M-1 for DIP to 80-300 M-1 for RA25. This order is identical with the reported biological activity of DIPD. For the protonated drugs in zwitterionic or neutral micelles the binding constants are reduced by a factor of 20-75.
Borissevitch
I E
IE
Instituto de Química de São Carlos, Universidade de São Paulo, Brasil.
Borges
C P
CP
Borissevitch
G P
GP
Yushmanov
V E
VE
Louro
S R
SR
Tabak
M
M
D001665:Binding Sites; D004176:Dipyridamole / Q000031:analogs & derivatives* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D015394:Molecular Structure; D012996:Solutions; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000737:chemistry*
D008823:Micelles; D012996:Solutions; D014665:Vasodilator Agents; D004176:Dipyridamole