Protein binding of quinolonecarboxylic acids. II. Spectral changes on the interaction of cinoxacin, nalidixic acid and pipemidic acid with human and rat albumins.

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Abstract
The interaction of cinoxacin (CINX), nalidixic acid (NA), and pipemidic acid (PPA) with human and rat serum albumins (HSA and RSA) was studied by UV difference absorption and circular dichroism (CD) spectroscopy. CINX and NA bound to the albumins and generated difference absorption and induced CD (ICD) spectra. The difference absorption spectral data explained resonably our previous observations that CINX bound to HSA more weakly than NA, but to RSA as strongly as NA. We used a quantity .DELTA..epsilon./.epsilon., designated as relative molar difference absorbance, at positions corresponding to the longest wavelength peaks in the difference spectra. The quantity was found to correlate linearly with percent bound to both HSA and RS, but with different slopes, from which the binding site for CINX and NA in RSA was supposed to provide a much more nonpolar environment than that in HSA. The magnitude of ICD bands observed at 371 nm for CINX and at 342-348 nm for NA corresponded to the binding degrees of these drugs to both albumins. Anisotropy factors for the ICD bands at 350-271 nm for CINX and 320-348 nm for NA were approximately similar between HSA and RSA, suggesting a similar ability to generate the ICD spectra in these wavelength regions upon binding to the albumins. Spectral results for PPA in albumin solutions showed little or no binding of this drug to HSA and RSA. PPA existed as a betaine form in neutral solution and its positively charged group acted as an unfavorable for binding to both albumins.