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MAO-B Inhibitor (2E)-3-(4-Bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one as a Neuroprotective Agent Against Alzheimer’s Disease

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Abstract

Chalcones (trans-1,3-diphenyl-2-propen-1-ones) form simple chemical structures that act as precursors for the biogenesis of flavonoids. These are distributed in plants and have two aromatic or heteroaromatic rings connected by a three-carbon α, β-unsaturated carbonyl group. Considering the importance of chalcones as monoamine oxidase and acetylcholinesterase inhibitors, the study was designed as a comprehensive and systematic analysis to evaluate the pharmacological activities leading to the formation of drug molecules against Alzheimer’s disease (AD). Based on our previous research, 11 indolyl chalcones (IC1–IC11) were synthesised and investigated for MAO-B inhibitory activity. The inhibitory potential was evaluated based on binding and reversibility studies using purified enzymes. The active and most promising molecule, (2E)-3-(4-bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one (IC9), also found predominant acetylcholinesterase inhibition and hence it was found dual acting in vitro. Based on this, the molecule IC9 was further subjected to cell line studies to further explore its role as a neuroprotective agent against neuronal degeneration, one of the main contributing parameters related to AD.

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Acknowledgements

The authors are thankful to AlMaarefa University for their support.

Funding

The authors have not disclosed any funding.

Author information

Author notes

  1. Rani Sasidharan and Ratheesh Mohanan contributed equally to this work.

Authors and Affiliations

  1. College of Pharmaceutical Sciences, Government Medical College, Thiruvananthapuram, Kerala, 695011, India

    Rani Sasidharan

  2. Department of Biochemistry, St. Thomas College, Pala, Kottayam, Kerala, 686574, India

    Ratheesh Mohanan

  3. School of Pharmacy, Graphic Era Hill University, Dehradun, Uttarakhand, 248007, India

    Neelima Kukreti

  4. St. Joseph’s College of Pharmacy, Cherthala, Kerala, 688524, India

    Praveen Raj

  5. Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, 72341, Sakaka, Saudi Arabia

    Mohamed A. Abdelgawad

  6. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt

    Mohamed A. Abdelgawad

  7. Department of Pharmacy Practice, College of Pharmacy, Al Maarefa University, 13713, Ad Diriyah, Saudi Arabia

    Mohammed M. Ghoneim

  8. Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt

    Mohammed M. Ghoneim

  9. Department of Chemistry, School of Advanced Sciences, VIT, Vellore, Tamil Nadu, 632014, India

    Sreedharannair L. Manju

  10. Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, 682 041, India

    Bijo Mathew

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  1. Rani Sasidharan
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Correspondence to Sreedharannair L. Manju or Bijo Mathew.

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Sasidharan, R., Mohanan, R., Kukreti, N. et al. MAO-B Inhibitor (2E)-3-(4-Bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one as a Neuroprotective Agent Against Alzheimer’s Disease. Neurochem Res 49, 1518–1528 (2024). https://doi.org/10.1007/s11064-023-04031-6

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