Rational design, synthesis, and enzymatic evaluation of spiroquinazoline derivatives as promising acetylcholinesterase inhibitors
DOI:
https://doi.org/10.60988/p.v38i1.295Keywords:
spiroquinazoline derivatives, Ellmans assay, Cholinesterase inhibitors, molecular docking, ADME, propertiesAbstract
Spiroquinazoline derivatives represent promising scaffolds for the development of novel anti-Alzheimer’s disease (AD) agents. In this study, three quinazoline derivatives (1–3) were synthesized from N-methylisatoic anhydride and fully characterized. Furthermore, we conducted in vitro anticholinesterase assays, molecular docking, and SwissADME predictions for the synthesized compounds. Compounds 1-3 were obtained in good yield, with compound 1 demonstrating potent inhibitory activity against acetylcholinesterase (AChE) (IC50 = 12.6 μg/mL). Thus, these compounds have potential for further development for use in Alzheimer's disease (AD) therapy. Future studies are required to elucidate whether compounds 1-3 have direct effects on Tau aggregation or Aβ production and to investigate their full therapeutic potential in the context of these predominant AD hypotheses.
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