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Synthesis and Biological Evaluation of Coumarin-Amino Acid-Benzotriazole Conjugates

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Abstract

Objective: It is aimed to synthesize new amino acid-conjugated coumarin-benzotriazole molecules and to investigate their acetylcholinesterase, urease, and lipase inhibition properties. Methods: Urease inhibitory activities of new compounds and standard were determined spectrophotometrically according to the method of Van Slykeand Archibald. The lipase activity assay was determined using the method of Bendicho. The acetylcholinesterase enzymatic activity was measured according to the method described by Ingkaninan. Results and Discussion: All synthesized compounds showed effective urease, lipase, and acetylcholinesterase inhibitory activities. Compound (Vd) has the most potent enzyme inhibition activity against urease with an IC50 = 0.038 ± 0.022 μM. Compound (Vc) has the most potent enzyme inhibition activity against lipase with an IC50 = 0.101 ± 0.046 μM. Compound (Ve) has the best inhibitory effect against acetylcholinesterase enzyme with an IC50 = 0.003 ± 0.001 μM. Conclusions: A novel series of coumarin-amino acid-benzotriazole conjugates have been synthesized, and their urease, lipase, and acetylcholinesterase (AChE) inhibitor activities were determined. Most of the tested compounds showed higher urease inhibitory activity IC50 values ranging from 0.038 ± 0.022 to 0.086 ± 0.057 µM than thiourea. Among the series, compound (Vc) proved to be the most potent showing lipase inhibitory activity with an IC50 = 0.101 ± 0.046 μM when compared to the standard inhibitor Orlistat with an IC50 = 0.185 ± 0.075 μM. Compounds (Ve), (VIa), (VId), and (VIe) were found to exhibit potent inhibitory properties against acetylcholinesterase enzyme in the range of IC50 = 0.003 ± 0.001–0.010 ± 0.006 μM when compared to the tacrine as standard (IC50 = 0.029 ± 0.012 μM).

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DATA AVAILABILITY

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by regular institutional funding, and no additional grants were obtained.

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Authors and Affiliations

  1. Department of Chemistry, Art and Science Faculty, Recep Tayyip Erdogan University, 53100, Rize, Turkey

    Emre Menteşe, Nedime Çalışkan & Gülay Akyüz

  2. Department of Chemistry, Faculty of Arts and Sciences, Giresun University, 28049, Giresun, Turkey

    Bahar Bilgin Sökmen

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  1. Emre MenteÅŸe
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  2. Nedime Çalışkan
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  3. Bahar Bilgin Sökmen
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  4. Gülay Akyüz
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Contributions

Author EM designed the experiments; authors EM and NÇ synthesized the samples. Authors EM and GA carried out studies using NMR spectroscopy. Authors BBS and GA made enzyme inhibition studies. Authors EM and GA contributed to manuscript preparation. All authors participated in the discussions.

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Correspondence to Emre MenteÅŸe.

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Menteşe, E., Çalışkan, N., Sökmen, B.B. et al. Synthesis and Biological Evaluation of Coumarin-Amino Acid-Benzotriazole Conjugates. Russ J Bioorg Chem 50, 191–200 (2024). https://doi.org/10.1134/S1068162024010126

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