Binding and Location of Dipyridamole Derivatives in Micelles: the Role of Drug Molecular Structure and Charge

Abstract

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-di-methyl-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 м-1 for DIP to 80-300 м-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.

Interaction of Chlorpromazine and Trifluoperazine with Anionic Sodium Dodecyl Sulfate (SDS) Micelles: Electronic Absorption and Fluorescence Studies

“…Biological membranes are extremely complex structures that require models of much less complexity to investigate different aspects of essential bilayer properties and functions (24,25), and micelles are a simplified model of the membranes, since they do not possess a bilayer structure and have in many cases an approximate spherical form. Thus the presence of polar and hydrophobic regions in their structures allows one to study the affinity of small molecules to membrane systems (13,14,26).…”

“…Despite the large amount of work aimed to understand the mechanisms of action of these drugs at the molecular level this question still remains unclear. For this reason, more information is necessary from model systems studies (13,14,(22)(23)(24)26).…”

“…SDS and a variety of other surfactants are commonly accepted as model systems for studying various aspects of membrane interactions with foreign molecules (13,14,23,26,33) including their localization. Electronic absorption spectroscopy makes it possible to determine pK a and K b (binding constant) values for the interacting molecules during an equilibrium process in solutions, and measurements of static fluorescence of pyrene and static fluorescence anisotropy of dipyridamole permits one to explore the nature of the aggregates formed by phenothiazine-detergent.…”

Electroreduction of dipyridamole at mercury-coated platinum microelectrode

“…Due to the low solubility of DIP in neutral media (15.0 µmol L -1 ) 25 and the low sensitivity of LSV technique, an investigation was carried out in solution of pH ranging from 1.5 to 4.5, where the solubility of the compound increases. Linear sweep voltammograms presented in Figure 6 show that when the pH is increased from 1.5 to 4.5, the first half-wave potentials shift to more cathodic values by ca.…”

Estudos da agregação de corantes ciânicos em soluções aquosas homogêneas e na presença de nanoestruturas

“…Devido à complexidade da estrutura da membrana, modelos simplificados desta são amplamente utilizados. Entre esses modelos, as micelas se apresentam como uma boa candidata para mimetizar as características estruturais da membrana [205][206][207].…”