Interaction of antithyroid drugs with bovine serum albumin: electrophoretic and fluorimetric study.

Abstract:

:The pre-equilibrium capillary zone electrophoretic (pre-eq CZE) method to determine association constants of active anionic forms of antithyroid drugs: 6-n-propyl-2-thiouracil (PTU), 6-methyl-2-thiouracil (MTU), 2-thiouracil (TU) with bovine serum albumin (BSA) under physiological pH 7.4 has been developed for the first time. Using the decrease of the selective electrochromatographic peak area of a drug anionic form due to binding with BSA the association constants K of the binary BSA complexes were calculated. It has been found that the binding constants (log K) of BSA with TU, MTU, and PTU are equal to 2.99, 1.85, and 2.11, respectively. The interaction of PTU, MTU, TU, 2-mercapto-1-methylimidazole (MMI), and ethyl-3-methyl-2-thionoimidazoline-1-carboxylate (Carb), which is considered to be a prodrug for MMI, with BSA has been investigated under physiological conditions by means of fluorescence spectroscopy. Fluorescence emission spectra of BSA in the presence of thioamides recorded at 295 nm excitation wavelength clearly show that the studied drugs act as quenchers, except MMI, which acts as quencher when being excited at 280 nm. The 295 nm light excites tryptophan residues, while the 280 nm light excites both tryptophan and tyrosine residues. The binding constants (log K) of BSA with PTU, MTU, TU, MMI, and Carb have been found to be 4.51, 4.30, 4.30, 2.64, and 4.32, respectively.

journal_name

J Pharm Sci

authors

Chernov'yants MS,Dolinkin AO,Chernyshev AV,Khohlov EV,Golovanova EG

doi

10.1002/jps.21915

subject

Has Abstract

pub_date

2010-03-01 00:00:00

pages

1567-73

issue

3

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(15)32738-6

journal_volume

99

pub_type

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