Inhibition of aldose reductase by 3',4'-dihydroxyflavones.

Abstract

A series of 3', 4'-dihydroxyflavones was assayed in vitro for inhibition of lens aldose reductase which has been implicated in the pathogenesis of sugar cataract. All the compounds tested were shown to be potent inhibitors of aldose reductase and 3', 4'-dihydroxy-5, 6, 7, 8-tetra-methoxyflavone (lens aldose reductase inhibitor 4, LARI 4), the most potent one, inhibited the enzymes from rat and bovine lenses by 50% at 3.2×10-8 and 1.7×10-7M, respectively. Inhibition of the enzyme by 3', 4'-dihydroxyflavones was non-competitive with respect to both DL-glyceraldehyde and reduced form of nicotinamide adenine dinucleotide phosphate. The inhibitory activities of 3', 4'-dihydroxyflavones against lens aldose reductase were pH-dependent, being maximal around pH 7.0.