Effects of non-steroid anti-inflammatory drugs in membrane bilayers.
The thermal effects of non-steroidal anti-inflammatory drugs (NSAIDs) meloxicam, tenoxicam, piroxicam and lornoxicam have been studied in dipalmitoylphosphatidylcholine (DPPC) membrane bilayers using neutral and acidic environments (pH 2.5). The strength of the perturbing effect of the drugs is summarized to a lowering of the main phase transition temperature and a broadening of the phase transition temperature as well as broadening or abolishment of the pretransition of DPPC bilayers. The thermal profiles in the two environments were very similar. Among the NSAIDs studied meloxicam showed the least perturbing effect. The differential scanning calorimetry results (DSC) in combination with molecular modeling studies point out that NSAIDs are characterized by amphoteric interactions and are extended between the polar and hydrophobic segments of lipid bilayers. The effects of NSAIDs in membrane bilayers were also investigated using Raman spectroscopy. Meloxicam showed a gauche:trans profile similar to DPPC bilayers while the other NSAIDs increased significantly the gauche:trans ratio. In conclusion, both techniques show that in spite of the close structural similarity of the NSAIDs studied, meloxicam appears to have the lowest membrane perturbing effects probably attributed to its highest lipophilicity.
Kyrikou
I
I
Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, Vasileos Constantinou 48, Athens 11635, Greece.
Hadjikakou
S K
SK
Kovala-Demertzi
D
D
Viras
K
K
Mavromoustakos
T
T
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry*; D000077239:Meloxicam; D008958:Models, Molecular; D015394:Molecular Structure; D010894:Piroxicam / Q000031:analogs & derivatives* / Q000737:chemistry; D013059:Spectrum Analysis, Raman; D013329:Structure-Activity Relationship; D013696:Temperature; D013843:Thiazines / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008051:Lipid Bilayers; D013843:Thiazines; D013844:Thiazoles; D010894:Piroxicam; D015060:1,2-Dipalmitoylphosphatidylcholine; C059451:lornoxicam; D000077239:Meloxicam; C032801:tenoxicam