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Anti-diabetic Properties of Calcium Channel Blockers: Inhibition Effects on Aldose Reductase Enzyme Activity

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Abstract

Aldose reductase (AR) belongs to NADPH-dependent oxidoreductases and converts glucose to sorbitol in the polyol pathway. AR inhibition is essential to prevent diabetic complications. Here, AR was purified from sheep kidney using simple methods and determined the interactions between some calcium channel blockers and the enzyme. It was found that calcium channel blockers (cinnarizine, nilvadipine, amlodipine besylate, nifedipine, isradipine, and nitrendipine) exhibit potential inhibitor properties for sheep kidney AR with IC50 values in the range of 5.87–8.77 μM and Ki constants in the range of 2.07 ± 0.72–5.62 ± 1.53 μM. The calcium channel blockers showed different inhibition mechanisms. It was determined that all studied compounds showed competitive inhibition effect except for isradipine and nitrendipine. They showed non-competitive inhibition. Among these drugs, cinnarizine was found to be the most potent AR inhibitor (Ki: 2.07 ± 0.72 μM). They may be useful in the treatment and/or prevention of diabetic complications.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Pharmacy, Erzincan Binali Yıldırım University, 24100, Erzincan, Turkey

    Cüneyt Türkeş

  2. Department of Chemistry, Faculty of Science, Atatürk University, 25240, Erzurum, Turkey

    Yeliz Demir

  3. Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470, Eskişehir, Turkey

    Şükrü Beydemir

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  1. Cüneyt Türkeş
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  2. Yeliz Demir
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Türkeş, C., Demir, Y. & Beydemir, Ş. Anti-diabetic Properties of Calcium Channel Blockers: Inhibition Effects on Aldose Reductase Enzyme Activity. Appl Biochem Biotechnol 189, 318–329 (2019). https://doi.org/10.1007/s12010-019-03009-x

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