Reversible inhibition of glucose transport in human erythrocytes by a series of pyridine derivatives.

A series of pyridine derivatives was chosen on the basis of structural similarity to glucose and to the hydrogen bonding capacity of this sugar. These compounds were found to reversibly inhibit glucose transport in a systematic fashion. The inhibition data can be rationalized by assuming that both competitive and noncompetitive binding sites exist on the cell membrane. The competitive site appears to have a much lower dissociation constant than the noncompetitive site for most derivatives. The effects of changes in substituents on the pyridine ring closely match, both in ring position and in the magnitude of the change in binding constant, those reported for derivatives of glucose. The stimulation of fluorodinitrobenzene inactivation of glucose transport by 2-amino-5-chloropyridine is in accord with this analysis. The strongest inhibitors bind about 100-fold more tightly than glucose itself. This series of pyridine compounds would appear to present a useful starting point for the development of site-specific irreversible inhibitors.