Inhibition profiles and molecular docking studies of antiproliferative agents against aldose reductase enzyme

Abstract

Inhibition of Aldose Reductase (AR) is very important in terms of preventing many diabetic complications such as retinopathy, neuropathy, and cataract. In this study, inhibition effects of some antiproliferative agents, which have been shown to have many biological activities besides their anticancer properties, on the AR enzyme, which is a diabetes-related enzyme, were investigated. Biochanin A compound with an IC50 value of 4.44 µM showed the best inhibition effect. IC50 values of Rhein, Betulinic acid, Sanguinarine chloride, Budesonide, Plumbagin and 2-Methoxyestradiol compounds were calculated as 7.87 µM, 7.45 µM, 19.25 µM, 21.00 µM, 28.87 µM and 38.5 µM, respectively. Molecular docking studies have also been conducted to elucidate the inhibition mechanisms of the compounds whose in vitro inhibition effects have been investigated, and the free binding energies of enzyme-inhibitor complexes have been calculated with the Molecular Mechanics Generalized Born Surface Area (MM-GBSA). Both experimental data and computer-aided calculations have revealed that the compounds studied are very important drug candidates aimed at preventing diabetic complications.

Keywords

• Aldose Reductase
• Antiproliferative
• Molecular Docking
• Inhibition

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