2. Academic Validation
  3. 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

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. 2023 Oct 9. doi: 10.1007/s11064-023-04031-6.
Rani Sasidharan # 1,  Ratheesh Mohanan # 2,  Neelima Kukreti 3,  Praveen Raj 4,  Mohamed A Abdelgawad 5 6,  Mohammed M Ghoneim 7 8,  Sreedharannair L Manju 9,  Bijo Mathew 10
Affiliations

Affiliations

  • 1 College of Pharmaceutical Sciences, Government Medical College, Thiruvananthapuram, Kerala, 695011, India.
  • 2 Department of Biochemistry, St. Thomas College, Pala, Kottayam, Kerala, 686574, India.
  • 3 School of Pharmacy, Graphic Era Hill University, Dehradun, Uttarakhand, 248007, India.
  • 4 St. Joseph's College of Pharmacy, Cherthala, Kerala, 688524, India.
  • 5 Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, 72341, Sakaka, Saudi Arabia.
  • 6 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt.
  • 7 Department of Pharmacy Practice, College of Pharmacy, Al Maarefa University, 13713, Ad Diriyah, Saudi Arabia.
  • 8 Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt.
  • 9 Department of Chemistry, School of Advanced Sciences, VIT, Vellore, Tamil Nadu, 632014, India. slmanju@vit.ac.in.
  • 10 Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, 682 041, India. bijomathew@aims.amrita.edu.
  • # Contributed equally.
PMID: 37814132 DOI: 10.1007/s11064-023-04031-6
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.

Keywords

Acetylcholinesterase; Alzheimer’s disease; Chalcones; Monoamine oxidase.

Figures
Products