Sanaa Aleed, Qais Abualassal , Zead Abudayeh

For correspondence:-  Qais Abualassal   Email: qais.abualassal@iu.edu.jo   Tel:00962-790906530

Received: 21 May 2024        Accepted: 2 November 2024        Published: 29 November 2024

Citation: Aleed S, Abualassal Q, Abudayeh Z. Synthesis and biological activities of novel spiroquinazoline derivatives for Alzheimer’s disease. Trop J Pharm Res 2024; 23(11):1879-1885 doi: 10.4314/tjpr.v23i11.11

© 2024 The authors.
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Abstract

Purpose: To synthesize novel spiroquinazoline derivatives and determine their biological properties as acetylcholinesterase (AChE) inhibitors and antioxidant agents. Methods: Several quinazoline derivatives (3-5) were synthesized using N-methylisatoic anhydride (1) as starting material. Synthesized compounds were fully characterized using thin-layer chromatography (TLC), mass spectroscopy (MS) and nuclear magnetic resonance (NMR) techniques. Furthermore, in vitro anticholinesterase and antioxidant activities of compound 5 were determined using Ellman’s and 1,1-diphenyl 2-picrylhydrazyl (DPPH) assays, respectively. Results: The synthesis resulted in a good yield of compound 5 (71 %), which demonstrated potent inhibitory effect on acetylcholinesterase enzyme (IC50 = 11.89 μmol/mL) and significant antioxidant activity (IC50 = 143.7 μmol/mL). Conclusion: The synthesized spiroquinazoline derivative 5 exhibits very good anti-AChE anticholinesterase and antioxidant activities. Thus, it has potential for further development for use in Alzheimer's disease (AD) therapy. Future studies are required to elucidate whether compound 5 has direct effects on Tau aggregation or Aβ production and to investigate its full therapeutic potential in the context of these predominant AD hypotheses.