Modification of the surface properties of membranes by any ligand could lead to several phenomena like aggregation, leakage of trapped contents or permeabilization, fusion, etc. Such modulation of surface properties is a fundamental requirement for many biological processes [1]. In this work, we present the synthesis and interaction of new piroxicam derivatives with model lipid bilayers.

The starting material for the synthesis of the above mentioned compounds was 1,1-dioxo-1,2-benzothiazol-3-one (saccharin). It was condensed with 2-bromo-4’-fluoroacetophenone in dimethylformamide (DMF) in the presence of triethylamine giving 1,1-dioxo-2-(4-fluorophenyl)acetyl-1,2-benzothiazol-3-one, which was then rearranged to the corresponding 1,2-benzothiazine ring. The final compounds were prepared by alkylation of corresponding 1,2-benzothiazine with 4-aryl/heteroaryl-1-(2-chloroacetyl/3-chloropropyl)piperazine giving four new structures (PD 28-31). The separated products were purified by the crystallization from ethanol. The structures of the compounds obtained were confirmed by elemental and spectral (IR, H¹NMR) analyses.

In spectroscopic experiments we assessed the influence of the examined new piroxicam derivatives on laurdan and prodan fluorescence in liposomes made of lecithin from egg yolk (EYPC) and dipalmitoylphosphatidylcholine (DPPC). Laurdan and prodan both possess the same fluorophore connected to an alkyl chain of different length (three carbon atoms in prodan and twelve in laurdan). Therefore prodan molecules locate closer to the hydrophilic surface of a bilayer than laurdan whose fluorophore is positioned close to phospholipid glycerol groups [2, 3].

PD 28-31 quenched the fluorescence of both laurdan and prodan. Additionally, the influence of PD 29 and PD 31 at 25 μM/l concentration on main DPPC phase transition was monitored by the use of laurdan generalized polarization.

In our present work we have shown that new piroxicam derivatives PD 28-31 interact with the model membranes under consideration.

References:

1. H. Chakraborty et al., Interaction of piroxicam with mitochondrial membrane and cytochrome c, Biochimica et Biophysica Acta 1768, 2007, 1138–1146.

2. E. Krasnowska et al., Prodan as a Membrane Surface Fluorescence Probe: Partitioning between Water and Phospholipid Phases, Biophysical Journal 74, 1998, 1984–1993.

3. L. Bagatolli et al., A Model for the Interaction of 6-Lauroyl-2-(N,N-dimethylamino)naphthalene with Lipid Environments: Implications for Spectral Properties, Photochemistry and Photobiology 70, 1999, 557-564.

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