Login Register Cart 0
Generic placeholder image

Current Organic Synthesis

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
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

Abstract

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.

« Previous Next »
Graphical Abstract

[1]
Lin, L.G.; Liu, Q.Y.; Ye, Y. Naturally occurring homoisoflavonoids and their pharmacological activities. Planta Med., 2014, 80(13), 1053-1066.
[2]
Jiang, H.B.; Huang, J.; Guo, M.J.; Zou, P.; Tian, X.Q. Recent advances in the study of natural homoisoflavonoids. Acta Pharm. Sin, 2007, 42(2), 118-126.
[3]
Rafi, M.M.; Vastano, B.C. Identification of a structure specific Bcl-2 phosphorylating homoisoflavone molecule from Vietnamese coriander (Polygonatum odoratum) that induces apoptosis and G2/M cell cycle arrest in breast cancer cell lines. Food Chem., 2007, 104(1), 332-340.
[4]
Alipour, E.; Mousavi, Z.; Safaei, Z.; Pordeli, M.; Safavi, M.; Firoozpour, L.; Mohammadhosseini, N.; Saeedi, M.; Ardestani, S.K.; Shafiee, A.; Foroumadi, A. Synthesis and cytotoxic evaluation of some new [1,3]dioxolo[4,5-g]chromen-8- one derivatives. Daru J. Pharm. Sci, 2014, 22(1), 41.
[5]
Zhou, C.X.; Zou, L.; Mo, J.X.; Wang, X.Y.; Yang, B.; He, Q.J.; Gan, L.S. Homoisoflavonoids from Ophiopogon japonicas. Helv. Chim. Acta, 2013, 96(7), 1203-1407.
[6]
Tait, S.; Salvati, A.L.; Desideri, N.; Fiore, L. Antiviral activity of substituted homoisoflavonoids on enteroviruses. Antiviral Res., 2006, 72(3), 252-255.
[7]
Hung, T.M.; Thu, C.V.; Dat, N.T.; Ryoo, S.W.; Lee, J.H.; Kim, J.C.; Na, M.; Jung, H.J.; Bae, K.; Min, B.S. Homoisoflavonoid derivatives from the roots of Ophiopogon japonicus and their in vitro anti-inflammation activity. Bioorg. Med. Chem. Lett., 2010, 20(8), 2412-2416.
[8]
Li, N.; Zhang, J.Y.; Zeng, K.W.; Zhang, L.; Che, Y.Y.; Tu, P.F. Anti-inflammatory homoisoflavonoids from the tuberous roots of Ophiopogon japonicas. Fitoterapia, 2012, 83(6), 1042-1045.
[9]
Shaikh, M.M.; Kruger, H.G.; Bodenstein, J.; Smith, P.; duToit, K. Anti-inflammatory activities of selected synthetic homoisoflavanones. Nat. Prod. Res., 2012, 26(16), 1473-1482.
[10]
Siddaiah, V.; Maheswara, M.; Rao, C.V.; Venkateswarlu, S.; Subbaraju, G.V. Synthesis, structural revision, and antioxidant activities of antimutagenic homoisoflavonoids from Hoffmanosseggia intricate. Bioorg. Med. Chem. Lett., 2007, 17(5), 1288-1290.
[11]
Wang, D.M.; Zeng, L.; Li, D.W.; Pu, W.J. Antioxidant activities of different extracts and homoisoflavanones isolated from the Polygonatum odoratum. Nat. Prod. Res., 2013, 27(12), 1111-1114.
[12]
Hu, C.M.; Kang, J.J.; Lee, C.C.; Li, C.H.; Liao, J.W.; Cheng, Y.W. Induction of vasorelaxation through activation of nitric oxide synthase in endothelial cells by brazilin. Eur. J. Pharmacol., 2003, 468(1), 37-45.
[13]
Basavarajappa, H.D.; Lee, B.; Lee, H.; Sulaiman, R.S.; An, H.C.; Magaña, C.; Shadmand, M.; Vayl, A.; Rajashekhar, G.; Kim, E.Y.; Suh, Y.G.; Lee, K.; Seo, S.Y.; Corson, T.W. Synthesis and biological evaluation of novel homoisoflavonoids for retinal neovascularization. J. Med. Chem., 2015, 58(12), 5015-5027.
[14]
Yempala, T.; Sriram, D.; Yogeeswari, P.; Kantevari, S. Molecular hybridization of bioactives: synthesis and antitubercular evaluation of novel dibenzofuran embodied homoisoflavonoids via Baylis-Hillman reaction. Bioorg. Med. Chem. Lett., 2012, 22(24), 7426-7430.
[15]
Zheng, G.X.; Zhang, Z.C.; Kang, B.R.; Yu, R.H.; Cao, Y.X.; Zhang, S.Q. Synthesis and vasodilatation of homoisoflavones. hin. J. Org. Chem, 2015, 35(5), 1112-1122.
[16]
Desideri, N.; Bolasco, A.; Fioravanti, R.; Monaco, L.P.; Orallo, F.; Yáñez, M.; Ortuso, F.; Alcaro, S. Homoisoflavonoids: natural scaffolds with potent and selective monoamine oxidase-B inhibition propertie. J. Med. Chem., 2011, 54(7), 2155-2164.
[17]
Sun, Y.; Chen, J.W.; Chen, X.M.; Huang, L.; Li, X.S. Inhibition of cholinesterase and monoamine oxidase-B activity by Tacrine-Homoisoflavonoid hybrids. Bioorg. Med. Chem., 2013, 21(23), 7406-7417.
[18]
Gan, C.S.; Zhao, Z.Z.; Nan, D.D.; Yin, B.B.; Hu, J.Y. Homoisoflavonoids as potential imaging agents for β-amyloid plaques in Alzheimer’s disease. Eur. J. Med. Chem., 2014, 76, 125-131.
[19]
Pourshojaei, Y.; Gouranourimi, A.; Hekmat, S.; Asadipour, A.; Rahmani-Nezhad, S.; Moradi, A.; Nadri, H.F.; Moghadam, H.; Emami, S.; Foroumadi, A.; Shafiee, A. Design, synthesis and anticholinesterase activity of novel benzylidenechroman-4-ones bearing cyclic amine side chain. Eur. J. Med. Chem., 2015, 97, 181-189.
[20]
Gan, L.S.; Zeng, L.W.; Li, X.R.; Zhou, C.X.; Li, J. New homoisoflavonoid analogues protect cells by regulating autophagy. Bioorg. Med. Chem. Lett., 2017, 27(6), 1441-1445.

Rights & Permissions Print Cite
Article Metrics
54
4
© 2024 Bentham Science Publishers | Privacy Policy