One of the most important factors affecting the distribution and the active concentration of many administered drugs is binding affinity for human serum albumin (HSA). In the bloodstream and tissue fluids, HSA serves as a vehicle for the transport of several endogenous compounds including unesterified fatty acids (FA), hemin, bilirubin and thyroxine all of which bind with high affinity.

       Long-chain fatty acids, a major source of cellular energy, are solubilized and transported in the blood by binding to serum albumin. Crystallographic studies of HSA have mapped at least seven FA binding sites and delineated the overlap with binding sites of some drugs and other endogenous compounds. The interactions of fatty acids with albumin modulates the ligand binding properties of protein  by inducing conformational changes in the binding sites I and II, respectively. Thereby, understanding albumin fatty acid interactions is of major clinical and pharmaceutical importance.

       In the circulation, HSA becomes nonenzymatically glycosylated by reducing sugars, and the reference range in normal humans is 6–10% glycoalbumin. However, this proportion typically increases to between 20% and 30% in hyperglycemic patients. The principal site of glycosylation of HSA is Lys-525, but the lysine residues in positions 199, 281 and 439 are also susceptible to modification. The effect of nonenzymatic glycosylation can influence on the affinity binding of drugs at site I (subdomain IIA) of albumin molecule.

       Meloxicam is pharmacologically important new generation, non-steroidal anti-inflammatory drug (NSAID) of enolic acid class compounds with a minimum adverse gastrointestinal and renal side effects associated with traditional NSAID [1].

The primary function of meloxicam is anti-inflammatory effect but they can also be used as agents in cancer treatment, because in various types of cancer, cyclooxygenase-2 is over expressed.  The nature of interaction of meloxicam with HSA involve strong drug–protein interactions with only high affinity site located in subdomain IIA [2,3].

The conformational changes associated with nonenzymatic glycosylation and FA binding may alter the physiological functions of albumin and binding of drugs.

       In the present paper the influence of myristic acid and the effect of nonenzymatic glycosylation on meloxicam binding to the albumin using fluorescence quenching method and circular dichroism spectroscopic technique were investigated. The studies have shown that the FA and nonenzymatic glycosylation induce conformational changes in the albumin molecule. These changes affect on the binding ability of meloxicam towards albumin.  The association constants in both cases were lower as compared to native protein.

 1. G. Dannhardt, W. Kiefer, Eur. J. Med. Chem. 36 (2001) 109-126

2. N. Seedher, S. Bhatia, J. Pharm. Biomed. Anal. 39 (2005) 257-262

3. L. Trynda-Lemiesz, K.Wiglusz , J. Pharm. Biomed. Anal. 52 (2010) 300–304

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