Structural changes of human serum albumin (HSA) caused by old age and coexisting diseases
result in differences in the binding of doxazosin (DOX). DOX is a postsynaptic α1- adrenoreceptor
antagonist used for treatment of hypertension and benign prostatic hyperplasia. In elderly people
suffering from various renal or hepatic diseases the significant portion of N-form of human serum albumin
(normal) is converted to A-form (aged). The differences in binding of doxazosin to N- and Aform
of albumin are an important factor, which may determines therapeutic dosage and toxicity of the
test drug. To indicate these differences, the technique of fluorescence spectroscopy was used. The association
constant (Ka) obtained from fluorescence quenching demonstrated that doxazosin has higher affinity for AHSA
than for HSA. In order to describe the cooperativity in binding process, the values of the Hill’s coefficient has been analysed.
For DOX-HSA system (λex 295 nm) Hill’s coefficient is close to 1 and it indicates that there is a single class of
binding sites. For DOX-HSA (λex 275 nm) and DOX-AHSA (λex 275 nm and λex 295 nm) systems we observed positive
cooperativity (nH>1). A greater red shift of fluorescence emission maximum of AHSA than HSA in the presence of DOX
was observed. This suggests that the binding of DOX to AHSA was accompanied by a stronger increase in polarity around
the fluorophores in comparison to HSA. The binding interaction between DOX and HSA has been also studied by molecular
Keywords: N-A transition, molecular aging, human serum albumin, doxazosin.
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