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Azomethine-clubbed thiazoles as human tissue non-specific alkaline phosphatase (h-TNAP) and intestinal alkaline phosphatase (h-IAP) Inhibitors: kinetics and molecular docking studies

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Abstract

Thiazole derivatives are known inhibitors of alkaline phosphatase, but various side effects have reduced their curative efficacy. Conversely, compounds bearing azomethine linkage display a broad spectrum of biological applications. Therefore, combining the two scaffolds in a single structural unit should result in joint beneficial effects of both. A new series of azomethine-clubbed thiazoles (3a–i) was synthesized and appraised for their inhibitory potential against human tissue non-specific alkaline phosphatase (h-TNAP) and human intestinal alkaline phosphatase (h-IAP). Compounds 3c and 3f were found to be most potent compounds toward h-TNAP with IC50 values of 0.15 ± 0.01 and 0.50 ± 0.01 µM, respectively, whereas 3a and 3f exhibited maximum potency for h-IAP with IC50 value of 2.59 ± 0.04 and 2.56 ± 0.02 µM, respectively. Molecular docking studies were also performed to find the type of binding interaction between potential inhibitor and active sites of enzymes. The enzymes inhibition kinetics studies were carried out to define the mechanism of enzyme inhibition. The current study leads to discovery of some potent inhibitors of alkaline phosphatase that is promising toward identification of compounds with druggable properties.

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Acknowledgements

Authors are thankful to the Higher Education Commission of Pakistan for the financial support.

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Authors and Affiliations

  1. Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan

    Aamer Saeed, Memona Javaid, Pervaiz Ali Channar & Ghulam Shabir

  2. Department of Pharmacy, Quaid-I-Azam University, Islamabad, 45320, Pakistan

    Arfa Tehzeeb

  3. Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan

    Syed Jawad Ali Shah & Jamshed Iqbal

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  1. Aamer Saeed
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  2. Memona Javaid
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  3. Syed Jawad Ali Shah
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  4. Pervaiz Ali Channar
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  5. Ghulam Shabir
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Correspondence to Aamer Saeed.

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Saeed, A., Javaid, M., Shah, S.J.A. et al. Azomethine-clubbed thiazoles as human tissue non-specific alkaline phosphatase (h-TNAP) and intestinal alkaline phosphatase (h-IAP) Inhibitors: kinetics and molecular docking studies. Mol Divers 26, 3241–3254 (2022). https://doi.org/10.1007/s11030-022-10385-w

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  • DOI: https://doi.org/10.1007/s11030-022-10385-w

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