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The therapeutic effect of BODIPY-based photosensitizers against acetylcholinesterase for the treatment of Alzheimer’s disease

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Abstract

The alzheimer disease (AD) origination and promulgation are closely associated with the acetylcholinesterase (AChE) enzyme. The management of AD involves the immediate usage of AChE inhibition drugs. To resolve this problem, two BODIPY-created cationic photosensitizers (PSs) have been developed, 1BDPC-Py and 1BDPC-TPP, for inhibition of AChE. Statistical analysis of the results revealed that both 1BDPC-Py (10–30 µM) and 1BDPC-TPP (15–40 µM) inhibited the AChE in a dose-dependent procedure. A kinetic study using the Lineweaver Burk plot showed that 1BDPC-Py a mixed type of inhibition, i.e., Vmax decreased and Km increased with increasing concentration of 1BDPC-Py, while 1BDPC-TPP caused an un-competitive type of inhibition i.e., both Km and Vmax decreased with an increase of 1BDPC-TPP concentrations. For 1BDPC-TPP the KIapp was found to increase from 15.61 to 37.83 (13.96–142.34%) while Vmaxiapp decreased from 307.97 to 440.52 (16.96–369.43.03%) with an increase of substrate from (0.05–1 mM), while for 1BDPC-TPP the Kmaxipp decreased from 106.73 to 19.25 (25.6–82%) and Vmaxiapp decreased from 246.54 to 131.55 (24.6–440.09%). The Ki, (inhibitory constant); KI, (constant of the dissociation constant), Km, (constant of Michaelis–Menten), and IC50 (50% inhibition) were found to be 15 µM, 24.186 µM, 0. 0.0537 mM, and 21.26 ± 0.15 µM for 1BDPC-Py and 22 µM, 41.91 µM, 0.312 mM, and 28.28 ± 0.12 µM for 1BDPC-TPP. The γKm (dissociation constant of the enzyme–substrate-inhibitor complex into substrate and enzyme-inhibitor complex) was found to be 0.083 µM. Thus, to the best of our information, both of these BODIPY-based PSs are the first excitable compounds in the treatment of alzheimer's disease.

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Acknowledgements

This work was financially supported by the Natural Science Foundation of China (22122701, 21731004, 21907050, 91953201, 21907044), the Natural Science Foundation of Jiangsu Province (BK20190282, BK20202004), and the Excellent Research Program of Nanjing University (ZYJH004).

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Authors and Affiliations

  1. Department of Biotechnology, University of Science and Technology, Bannu, KPK, Pakistan

    Mushtaq Ahmed, Naila Sher & Rahmat Ali Khan

  2. Department of Botany, University of Science and Technology, Bannu, KPK, Pakistan

    Nadia Mushtaq

  3. State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Coordination Chemistry Institute, Nanjing University, Nanjing, 210093, People’s Republic of China

    Muhammad Amir Masood

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Ahmed, M., Mushtaq, N., Sher, N. et al. The therapeutic effect of BODIPY-based photosensitizers against acetylcholinesterase for the treatment of Alzheimer’s disease. J Proteins Proteom (2024). https://doi.org/10.1007/s42485-024-00137-9

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