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Identification of the Inhibition Effects of Some Natural Antiproliferative Agents on CA-I, CA-II, and AChE Activities Isolated from Human Erythrocytes by Kinetic and Molecular Docking Studies

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Abstract

Nowadays the determination of inhibitors of carbonic anhydrase isoenzymes (CAs) have become one of the main goals of drug design studies, and inhibitors of CAs have taken their place in clinical applications to be used in the treatment and diagnosis of many diseases from glaucoma to cancer. On the other hand, acetylcholinesterase (AChE) inhibitors are also the main target molecules for the treatment of Alzheimer’s disease. However, the unwanted side effects of existing CA and AChE inhibitors necessitate the identification of new and selective inhibitors of these enzymes. In this study, we examined the inhibition effects of some natural antiproliferative agents on CA-I, CA-II, and AChE activities isolated from human erythrocytes. Betulinic acid (I) had the strongest inhibitory effect on esterase activity of hCA-I (IC50 29.16 µM) and hCA-II (IC50 31.82 µM). On the other hand, sanguinarine chloride (VI) had the strongest inhibitory effect (IC50: 19.44 µM) on hAChE activity. Molecular modeling studies were also carried out to elucidate the inhibition mechanism of betulinic acid on hCA-I and hCA-II isoenzymes and sanguinarine chloride on the hAChE enzyme. We believe that the results we obtained in this study will contribute to the design of new and natural CA and AChE inhibitors.

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Funding

The authors thank to Igdir University Research Fund Accounting for their support to carry out this work (project no. 2020-SBE-A03).

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Authors and Affiliations

  1. Iğdır University, Vocational School of Health Services, Department of Medical Services and Techniques, 76000, Iğdır, Turkey

    N. Kılınç

  2. Iğdır University, Faculty of Engineering, Food Engineering, Iğdır University, 76000, Iğdır, Turkey

    U. Güller

  3. Kırşehir Ahi Evran University, Faculty of Science and Arts, Department of Chemistry, 40100, Kırşehir, Turkey

    Z. Alım

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  1. N. Kılınç
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Correspondence to Z. Alım.

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Healthy human erythrocytes used in this study were obtained from Atatürk University blood center. Other than that, it does not include any studies involving human participants by any of the authors, and does not include any animal studies performed by any author.

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Kılınç, N., Güller, U. & Alım, Z. Identification of the Inhibition Effects of Some Natural Antiproliferative Agents on CA-I, CA-II, and AChE Activities Isolated from Human Erythrocytes by Kinetic and Molecular Docking Studies. Russ J Bioorg Chem 48, 720–730 (2022). https://doi.org/10.1134/S1068162022040124

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