Journal of the Iranian Chemical Society

, Volume 15, Issue 7, pp 1457–1466 | Cite as

Synthesis of some quinazolinone derivatives using magnetic nanoparticles-supported tungstic acid as antimicrobial agents

  • Masoumeh Divar
  • Kamiar Zomorodian
  • Sorayya Bastan
  • Somayeh Yazdanpanah
  • Soghra Khabnadideh
Original Paper


Quinazolinones are appealing materials because of their precious biological effects. In this study 10 new quinazolinone derivatives (4a4j) were synthesized via an efficient three-component condensation reaction between anthranilic acid, acetic anhydride and different amines. This process was carried out for the first time in the presence of catalytic amount of magnetic nanoparticle supported tungstic acid, under solvent-free condition. The acidic catalyst can be easily reusing by an outward magnetic field after completion the reaction without any uncleanness. Chemical structures of the products were confirmed by spectroscopic methods such as: 1HNMR and 13CNMR, IR and elemental analysis. Antifungal and antibacterial activities were evaluated against different species of microorganisms including gram positive and gram negative bacteria as well as fungi. Broth microdilution method as recommended by clinical and laboratory standard institute was used for this purpose. The results show compounds 4h had the best antibacterial and antifungal activity against the examined bacteria and fungi. Compounds 4ad and 4f also showed good activity against some species.

Graphical Abstract

Synthesis of quinazoline derivatives as antimicrobial agents in the presence of MNP-TA


Quinazolinone Synthesis Antimicrobial Antifungal 



Financial assistance from the Shiraz University of Medical Sciences by way of grant number 94-01-36-9621 is gratefully acknowledged.

Supplementary material

13738_2018_1337_MOESM1_ESM.docx (2.5 mb)
Supplementary material 1 (DOCX 2510 kb)


  1. 1.
    W. Armarego, Quinazolines. Adv. Heterocycl. Chem. 24, 1–62 (1979)CrossRefGoogle Scholar
  2. 2.
    D.J. Connolly, D. Cusack, T.P. O’Sullivan, P.J. Guiry, Synthesis of quinazolinones and quinazolines. Tetrahedron 61(43), 10153–10202 (2005)CrossRefGoogle Scholar
  3. 3.
    A. D’yakonov, M. Telezhenetskaya, Quinazoline alkaloids in nature. Chem. Nat. Compd. 33(3), 221–267 (1997)CrossRefGoogle Scholar
  4. 4.
    S. Johne, The Quinazoline Alkaloids. Fortschritte der Chemie organischer Naturstoffe/Progress in the Chemistry of Organic Natural Products (Springer, Berlin, 1984), pp. 159–229CrossRefGoogle Scholar
  5. 5.
    A. Witt, J. Bergman, Recent developments in the field of quinazoline chemistry. Curr. Org. Chem. 7(7), 659–677 (2003)CrossRefGoogle Scholar
  6. 6.
    A. Moghimi, R.H. Khanmiri, I. Omrani, A. Shaabani, A new library of 4(3H)- and 4,4′(3H,3H′)-quinazolinones and 2-(5-alkyl-1,2,4-oxadiazol-3-yl)quinazolin-4(3H)-one obtained from diaminoglyoxime. Tetrahedron Lett. 54(30), 3956–3959 (2013)CrossRefGoogle Scholar
  7. 7.
    P.V. Acharyulu, P. Dubey, P. Prasada Reddy, T. Suresh, Synthesis of new 4 (3H)-quinazolinone derivatives under solvent-free conditions using PEG-400. ARKIVOC 11(3), 104–111 (2008)Google Scholar
  8. 8.
    S. Jiang, Q. Zeng, M. Gettayacamin, A. Tungtaeng, S. Wannaying, A. Lim et al., Antimalarial activities and therapeutic properties of febrifugine analogs. Antimicrob. Agents Chemother. 49(3), 1169–1176 (2005)CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    A. Amin, D. Mehta, S. Samarth, Biological Activity in the Quinazolone Series. Progress in Drug Research/Fortschritte der Arzneimittelforschung/Progrès des recherches pharmaceutiques (Springer, Berlin, 1970), pp. 218–268Google Scholar
  10. 10.
    P.P. Bandekar, K.A. Roopnarine, V.J. Parekh, T.R. Mitchell, M.J. Novak, R.R. Sinden, Antimicrobial activity of tryptanthrins in Escherichia coli. J. Med. Chem. 53(9), 3558–3565 (2010)CrossRefPubMedGoogle Scholar
  11. 11.
    J. Bergman, S. Bergman, Studies of rutaecarpine and related quinazolinocarboline alkaloids. J. Org. Chem. 50(8), 1246–1255 (1985)CrossRefGoogle Scholar
  12. 12.
    N. Coşkun, M. Çetin, Synthesis of 2-aryl-1, 2, 3, 4-tetrahydroquinazolin-1-ols and their conversion to 7-aryl-9H-6-oxa-5, 8-diaza-benzocycloheptenes. Tetrahedron Lett. 45(49), 8973–8975 (2004)CrossRefGoogle Scholar
  13. 13.
    A. Kamal, K.V. Ramana, M.V. Rao, Chemoenzymatic synthesis of pyrrolo [2, 1-b] quinazolinones: lipase-catalyzed resolution of vasicinone. J. Org. Chem. 66(3), 997–1001 (2001)CrossRefPubMedGoogle Scholar
  14. 14.
    N.P. McLaughlin, P. Evans, Dihydroxylation of vinyl sulfones: stereoselective synthesis of (+)- and (−)-febrifugine and halofuginone. J. Org. Chem. 75(2), 518–521 (2009)CrossRefGoogle Scholar
  15. 15.
    H.-B. Zhou, G.-S. Liu, Z.-J. Yao, Short and efficient total synthesis of luotonin A and 22-hydroxyacuminatine using a common cascade strategy. J. Org. Chem. 72(16), 6270–6272 (2007)CrossRefPubMedGoogle Scholar
  16. 16.
    E. Jafari, M.R. Khajouei, F. Hassanzadeh, G.H. Hakimelahi, G.A. Khodarahmi, Quinazolinone and quinazoline derivatives: recent structures with potent antimicrobial and cytotoxic activities. Res. Pharm. Sci. 11(1), 1 (2016)PubMedPubMedCentralGoogle Scholar
  17. 17.
    T.P. Selvam, P.V. Kumar, Quinazoline marketed drugs. Res. Pharm. 1(1), 1–21 (2015)Google Scholar
  18. 18.
    R.J. Abdel-Jalil, W. Voelter, M. Saeed, A novel method for the synthesis of 4(3H)-quinazolinones. Tetrahedron Lett. 45(17), 3475–3476 (2004)CrossRefGoogle Scholar
  19. 19.
    V. Alagarsamy, A. Thangathiruppathy, S. Rajasekaran, S. Vijaykumar, R. Revathi, J. Anburaj et al., Pharmacological evaluation of 2-substituted (1, 3, 4) thiadiazolo quinazolines. Indian J. Pharm. Sci. 68(1), 108 (2006)CrossRefGoogle Scholar
  20. 20.
    G. Khodarahmi, E. Jafari, G. Hakimelahi, D. Abedi, M.R. Khajouei, F. Hassanzadeh, Synthesis of some new quinazolinone derivatives and evaluation of their antimicrobial activities. Iran. J. Pharm. Res. IJPR 11(3), 789 (2012)PubMedGoogle Scholar
  21. 21.
    K. Natte, H. Neumann, X.-F. Wu, Pd/C as an efficient heterogeneous catalyst for carbonylative four-component synthesis of 4 (3H)-quinazolinones. Catal. Sci. Technol. 5(9), 4474–4480 (2015)CrossRefGoogle Scholar
  22. 22.
    A. Khalafi-Nezhad, M. Divar, F. Panahi, Magnetic nanoparticles-supported tungstic acid (MNP-TA): an efficient magnetic recyclable catalyst for the one-pot synthesis of spirooxindoles in water. RSC Adv. 5(3), 2223–2230 (2015)CrossRefGoogle Scholar
  23. 23.
    M. Dabiri, S.C. Azimi, H.R. Khavasi, A. Bazgir, A novel reaction of 6-amino-uracils and isatins. Tetrahedron 64(30), 7307–7311 (2008)CrossRefGoogle Scholar
  24. 24.
    M.M. Heravi, M. Vazin Fard, Z. Faghihi, Heteropoly acids-catalyzed organic reactions in water: doubly green reactions. Green Chem. Lett. Rev. 6(4), 282–300 (2013)CrossRefGoogle Scholar
  25. 25.
    H. Sharghi, M. Jokar, Al2O3/MeSO3H: a novel and recyclable catalyst for one-pot synthesis of 3, 4-dihydropyrimidinones or their sulfur derivatives in Biginelli condensation. Synth. Commun.®. 2009;39(6):958–979Google Scholar
  26. 26.
    A. Maleki, A.A. Jafari, S. Yousefi, MgFe2O4/cellulose/SO3H nanocomposite: a new biopolymer-based nanocatalyst for one-pot multicomponent syntheses of polysubstituted tetrahydropyridines and dihydropyrimidinones. J. Iran. Chem. Soc. 14(8), 1801–1813 (2017)CrossRefGoogle Scholar
  27. 27.
    A. Maleki, M. Aghaei, R. Paydar, Highly efficient protocol for the aromatic compounds nitration catalyzed by magnetically recyclable core/shell nanocomposite. J. Iran. Chem. Soc. 14(2), 485–490 (2017)CrossRefGoogle Scholar
  28. 28.
    A. Khalafi-Nezhad, S.M. Haghighi, A. Purkhosrow, F. Panahi, An efficient one-pot accessto quinazolinone derivatives using TiO2 nanoparticles as catalyst: synthesis and vasorelaxant activity evaluation. Synlett 23(06), 920–924 (2012)CrossRefGoogle Scholar
  29. 29.
    A. Khalafi-Nezhad, F. Panahi, Synthesis of new dihydropyrimido [4, 5-b] quinolinetrione derivatives using a four-component coupling reaction. Synthesis 6, 984–992 (2011)CrossRefGoogle Scholar
  30. 30.
    A. Khalafi-Nezhad, M. Divar, F. Panahi, Nucleosides as reagents in multicomponent reactions: one-pot synthesis of heterocyclic nucleoside analogues incorporating pyrimidine-fused rings. Tetrahedron Lett. 54(3), 220–222 (2013)CrossRefGoogle Scholar
  31. 31.
    A. Khalafi-Nezhad, M. Divar, F. Panahi, Synthesis of α-aminonitriles with benzimidazolic and theophyllinic backbones using the strecker reaction. J. Org. Chem. 78(21), 10902–10908 (2013)CrossRefPubMedGoogle Scholar
  32. 32.
    M. Divar, F. Panahi, S.R. Shariatipour, A. Khalafi‐Nezhad, Synthesis of imidazole and theophylline derivatives incorporating pyrimidine‐fused heterocycles using magnetic nanoparticles‐supported tungstic acid (MNP‐TA) catalyst. J. Heterocycl. Chem. 54(1), 660–669 (2016)CrossRefGoogle Scholar
  33. 33.
    National Committee for Clinical Laboratory S, Reference Methods for Broth Dilution Antifungal Susceptibility Testing of Yeast: Approved Standar (National Committee for Clinical Laboratory Standards, Wayne, 2002)Google Scholar
  34. 34.
    Standards NCfCL, Reference Methods for Broth Dilution Antifungal Susceptibility Testing of Yeast: Approved Standar (National Committee for Clinical Laboratory Standards, Wayne, 2002)Google Scholar
  35. 35.
    M.J. Ferraro, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically (NCCLS, Wayne, 2000)Google Scholar
  36. 36.
    B. Karami, V. Ghashghaee, S. Khodabakhshi, Novel silica tungstic acid (STA): preparation, characterization and its first catalytic application in synthesis of new benzimidazoles. Catal. Commun. 20, 71–75 (2012)CrossRefGoogle Scholar
  37. 37.
    G.B. Payne, C.W. Smith, Reactions of hydrogen peroxide. III. Tungstic acid catalyzed hydroxylation of cyclohexene in nonaqueous media. J. Org. Chem. 22(12), 1682–1685 (1957)CrossRefGoogle Scholar
  38. 38.
    N. Ahmed, Z.N. Siddiqui, Sulphated silica tungstic acid as a highly efficient and recyclable solid acid catalyst for the synthesis of tetrahydropyrimidines and dihydropyrimidines. J. Mol. Catal. A Chem. 387, 45–56 (2014)CrossRefGoogle Scholar
  39. 39.
    M. Farahi, B. Karami, S. Alipour, L.T. Moghadam, Silica tungstic acid as an efficient and reusable catalyst for the one-pot synthesis of 2-amino-4H-chromene derivatives. Acta Chim. Slov. 61, 94–99 (2014)PubMedGoogle Scholar
  40. 40.
    S. Dhein, A. Salameh, R. Berkels, W. Klaus, Dual mode of action of dihydropyridine calcium antagonists. Drugs 58(3), 397–404 (1999)CrossRefPubMedGoogle Scholar
  41. 41.
    B. Meunier, Hybrid molecules with a dual mode of action: dream or reality?†. Acc. Chem. Res. 41(1), 69–77 (2007)CrossRefPubMedGoogle Scholar

Copyright information

© Iranian Chemical Society 2018

Authors and Affiliations

  1. 1.Pharmaceutical Sciences Research CenterShiraz University of Medical SciencesShirazIran
  2. 2.Department of Parasitology and Mycology, Faculty of MedicineShiraz University of Medical SciencesShirazIran

Personalised recommendations