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Current Organic Synthesis


ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

Research Article

Synthesis and Neuroprotective Biological Evaluation of Quinazolinone Derivatives via Scaffold Hopping

Author(s): Fan Yang, Wei-Ping He, Jia-Qi Yao, Dong Zou, Pu Chen and Jie Li*

Volume 16, Issue 5, 2019

Page: [772 - 775] Pages: 4

DOI: 10.2174/1570179416666190328233501

Price: $65


Objective: To develop efficient method for the synthesis of quinazolinone derivatives bearing different functional groups on ring A and ring B and evaluation as neuroprotective agents.

Methods: Synthetic route to quinazolinone derivatives was furnished by condensation/cyclocondensation/ reduction sequence of the activated N-acylbenzotriazoles. The structures of the targets compounds have been deduced upon their spectral data (1HNMR, 13CNMR and Mass spectroscopy). The neuroprotective activities of the synthesized compounds are also evaluated.

Results: Preliminary screening on a MPP+ induced SH-SY5Y cell injury model of the synthesized compounds resulted in four compounds (6q, 6r, 6u, and 8e) showed promising neural cell protection activities. The action mechanisms of these compounds on neuroprotection were then analyzed by docking and reverse docking modeling.

Conclusion: A series of quinazolinone derivatives, including different substitution types on rings A and B were designed and synthesized via scaffold hopping. With the help of neuroprotective biological evaluation, several efficient therapeutic neuroprotective agents were found for further evaluation as drug candidate against neurodegenerative disorder.

Keywords: Homoisoflavonoid, scaffold hopping, quinazolinone, neuroprotection, autophagy, neuroprotective agents.

Graphical Abstract
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