Chemical Papers

, Volume 72, Issue 4, pp 1041–1053 | Cite as

New series of quinazolinone derived Schiff’s bases: synthesis, spectroscopic properties and evaluation of their antioxidant and cytotoxic activity

  • Zuzana Hricovíniová
  • Michal Hricovíni
  • Katarína Kozics
Original Paper

Abstract

A series of novel 2,3-di-substituted-2,3-dihydro-quinazolin-4(1H)-one derived Schiff’s bases (17) have been designed, synthesized and characterized on the basis of their physical and spectral data. The presented microwave-assisted, phosphomolybdic acid (PMoA) catalysed, protocol provides an efficient and convenient route for the synthesis of structurally diverse and potentially biologically active compounds. The molecular structures of these Schiff’s bases related to quinazolinones were confirmed by various spectroscopic methods (NMR, FTIR, UV–Vis) and their antioxidant activities were evaluated by UV–Vis and EPR spectroscopy employing 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay. Derivatives 17 were examined for their cytotoxicity in vitro against human hepatocellular carcinoma cells (HepG2) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphentltetrazolium bromide (MTT) assay. The structure–activity relationships study revealed that the position and nature of functional groups attached to the quinazolinone moiety alter their physico-chemical and biological properties. Derivatives 5, 6 and 7 bearing multiple electron-donating groups were found to be the most active members of this series.

Keywords

Quinazolinones Heterogeneous catalysis NMR EPR spectroscopy Antioxidant Cytotoxic effect 

Notes

Acknowledgements

The authors would like to acknowledge financial support from the Slovak Grant Agency, VEGA Grants No. 2/0100/14, 1/0041/15, 2/0027/16, 2/0022/18 and SP Grant 2003SP200280203 supported by the Research & Development Operational Program funded by the ERDF.

Supplementary material

11696_2017_345_MOESM1_ESM.docx (699 kb)
Supplementary material 1 (DOCX 698 kb)

References

  1. Berridge MV, Herst PM, Tan AS (2005) Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Ann Rev 11:127–152.  https://doi.org/10.1016/S1387-2656(05)11004-7 CrossRefGoogle Scholar
  2. Besson T, Chosson E (2007) Microwave-assisted synthesis of bioactive quinazolines and quinazolinones. Comb Chem High Throughput Screen 10:903–917.  https://doi.org/10.2174/138620707783220356 CrossRefGoogle Scholar
  3. Blevins AA, Blanchard GJ (2004) Effect of positional substitution on the optical response of symmetrically disubstituted azobenzene derivatives. J Phys Chem B 108:4962–4968.  https://doi.org/10.1021/jp037436w CrossRefGoogle Scholar
  4. Brees KD, Lamѐthe JF, DeArmitt C (2000) Improving synthetic hindered phenol antioxidants:learning from vitamin E. Polym Degrad Stab 70:89–96.  https://doi.org/10.1016/S0141-3910(00)00094-X CrossRefGoogle Scholar
  5. Chawla A, Batra Ch (2013) Recent advances of quinazolinone derivatives as marker for various biological activities. Int Res J Pharm 4:49–58.  https://doi.org/10.7897/2230-8407.04309 CrossRefGoogle Scholar
  6. Cozzi PG (2004) Metal-Salen schiff base complexes in catalysis: practical aspects. Chem Soc Rev 33:410–421.  https://doi.org/10.1039/B307853C CrossRefGoogle Scholar
  7. Crompton EM, Lewis FD (2004) Positional effects of the hydroxy substituent on the photochemical and photophysical behavior of 3- and 4-hydroxystilbene. Photochem Photobiol Sci 3:660–668.  https://doi.org/10.1039/b403661a CrossRefGoogle Scholar
  8. Da Silva CM, Da Silva DL, Modolo LV, Alves RB, De Resende MA, Martins CVB, De Fatima A (2011) Schiff bases: a short review of their antimicrobial activities. J Adv Res 2:1–8.  https://doi.org/10.1016/j.jare.2010.05.004 CrossRefGoogle Scholar
  9. Díaz MS, Freile ML, Gutiérrez MI (2009) Solvent effect on the UV/Vis absorption and fluorescence spectroscopic properties of berberine. Photochem Photobiol Sci 8:970–974.  https://doi.org/10.1039/b822363g CrossRefGoogle Scholar
  10. Ernst OP, Lodowski DT, Elstner M, Hegemann P, Brown LS, Kandori H (2014) Microbial and animal rhodopsins: structures, functions, and molecular mechanisms. Chem Rev 114:126–163.  https://doi.org/10.1021/r4003769c CrossRefGoogle Scholar
  11. Firouzabadi H, Jafari AA (2005) Heteropoly acids, their salts and polyoxometalates as heterogenous, efficient and eco-friendly catalysts in organic reactions: Some recent advances. J Iran Chem Soc 2:85–114.  https://doi.org/10.1007/BF03247201 CrossRefGoogle Scholar
  12. Fülöp F, Simeonov M, Pihlaja K (1992) Formation of 1,2-dihydroquinazolin-4(3H)-ones. Reinvestigation of a recently reported 1,3,-4-benzotriazepine synthesis. Tetrahedron 48:531–538.  https://doi.org/10.1016/S0040-4020(01)89014-1 CrossRefGoogle Scholar
  13. Gawad ANM, Georgey HH, Youssef RM, El-sayed NA (2010) Synthesis and antitumor activity of some 2,3-disubstituted quinazolin-4(3H)-ones and 4,6-disubstituted-1,2,3,4 tetrahydroquinazolin-2H-ones. Eur J Med Chem 45:6058–6067.  https://doi.org/10.1016/j.ejmech.2010.10.008 CrossRefGoogle Scholar
  14. Guo Z, Xing R, Liu S, Zhong Z, Ji X, Wang L, Li P (2007) Antifungal properties of Schiff bases of chitosan, N-substituted chitosan and quaternized chitosan. Carbohydr Res 342:1329–1332.  https://doi.org/10.1016/j.carres.2007.04.006 CrossRefGoogle Scholar
  15. Halliwell B, Gutteridge JMC (1999) Free radicals in biology and medicine, 3rd edn. Clarendon Press, OxfordGoogle Scholar
  16. Hricovíni M, Hricovíni M (2017) Photochemically-induced anti-syn isomerization of quinazolinone-derived Schiff’s bases: EPR, NMR and DFT analysis. Tetrahedron 73:252–261.  https://doi.org/10.1016/j.tet.2016.12.011 CrossRefGoogle Scholar
  17. Hricovíniová Z (2006) The effect of microwave irradiation on Mo(VI) catalysed transformations of reducing saccharides. Carbohydr Res 341:2131–2134.  https://doi.org/10.1016/j.carres.2006.05.007 CrossRefGoogle Scholar
  18. Hricovíniová Z (2010) A new approach to Amadori ketoses via Mo(VI)-catalyzed stereospecific isomerization of 2-C-branched sugars bearing azido function in a microwave field. Tetrahedron Asymm 21:2238–2243.  https://doi.org/10.1016/j.tetasy.2010.07.027 CrossRefGoogle Scholar
  19. Hricovíniová Z (2016) Surfactants of biological origin: the role of MO(VI) and microwaves in the synthesis of xylan-based non-ionic surfactants. Carbohydr Polym 144:297–304.  https://doi.org/10.1016/j.carbpol.2016.02.070 CrossRefGoogle Scholar
  20. Kajiyama T, Ohkatsu Y (2001) Effect of para-substitutes of phenolic antioxidants. Polym Degrad Stab 71:445–452.  https://doi.org/10.1016/S0141-3910(00)00196-8 CrossRefGoogle Scholar
  21. Kaur H, Limb SM, Ramasamy K, Vasudevan M, Shah SAA, Narasimhan B (2017) Diazenyl schiff bases: synthesis, spectral analysis, antimicrobial studies and cytotoxic activity on human colorectal carcinoma cell line (HCT-116). Arab J. Chem.  https://doi.org/10.1016/j.arabjc.2017.05.004 Google Scholar
  22. Khan MTH, Khan R, Wuxiuer Y, Arfan M, Ahmed M, Sylte I (2010) Identification of novel quinazolin-4 (3H)-ones as inhibitors of thermolysin, the prototype of the M4 family of proteinases. Bioorg Med Chem 18:4317–4327.  https://doi.org/10.1016/j.bmc.2010.04.083 CrossRefGoogle Scholar
  23. Kozhevnikov IV (1998) Catalysis by heteropoly acids and multicomponent polyoxometalates in liquid-phase reactions. Chem Rev 98:171–198.  https://doi.org/10.1021/cr960400y CrossRefGoogle Scholar
  24. Kumar A, Sharma P, Kumari P, Lal Kalal B (2011) Exploration of antimicrobial and antioxidant potential of newly synthesized 2,3-disubstituted quinazoline-4(3H)-ones. Bioorg Med Chem Lett 21:4353–4357.  https://doi.org/10.1016/j.bmcl.2011.05.031 CrossRefGoogle Scholar
  25. Kuntikana S, Bhat C, Kongot M, Bhat S, Kumar A (2016) An expeditious green cascade synthesis of 3-Arylideneaminoquinazolin-4(1H)-one derivatives via ‘solvent drop grinding’ and their antioxidant and dna protective studies. Chem Select 1:1723–1728.  https://doi.org/10.1002/slct.201600362 Google Scholar
  26. Loupy A (2006) Microwaves in Organic Synthesis. Wiley-VCHGoogle Scholar
  27. Martins MAP, Frizzo CP, Moreira DN, Buriol L, Machado P (2009) Solvent-Free Heterocyclic Synthesis. Chem Rev 109:4140–4182.  https://doi.org/10.1021/cr9001098 CrossRefGoogle Scholar
  28. Mhaske SB, Argade NP (2006) The chemistry of recently isolated naturally occurring quinazolinone alkaloids. Tetrahedron 62:9787–9826.  https://doi.org/10.1016/j.tet.2006.07.098 CrossRefGoogle Scholar
  29. Michael JP (2005) Quinoline, quinazoline and acridone alkaloids. Nat Prod Rep 22:627–646.  https://doi.org/10.1039/B413750G CrossRefGoogle Scholar
  30. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63.  https://doi.org/10.1016/0022-1759(83)90303-4 CrossRefGoogle Scholar
  31. Nielsen IB, Petersen MÅ, Lammich L, Nielsen MB, Andersen LH (2006) Absorption studies of neutral retinal schiff base chromophores. J Phys Chem A 110:12592–12596.  https://doi.org/10.1021/jp064901r CrossRefGoogle Scholar
  32. Przybylski P, Huczynski A, Pyta K, Brzezinski B, Bartl F (2009) Biological properties of schiff bases and azo derivatives of phenols. Curr Org Chem 13:124–148.  https://doi.org/10.2174/138527209787193774 CrossRefGoogle Scholar
  33. Rakesh KP, Manukumar HM, Channe Gowda D (2015) Schiff’s bases of quinazolinone derivatives: synthesis and SAR studies of a novel series of potential anti-inflammatory and antioxidants. Bioorg Med Chem Lett 25:1072–1077.  https://doi.org/10.1016/j.bmcl.2015.01.010 CrossRefGoogle Scholar
  34. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C (1999) Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med 26:1231–1237.  https://doi.org/10.1016/S0891-5849(98)00315-3 CrossRefGoogle Scholar
  35. Sawant VA, Yamgar BA, Sawant SK, Chavan SS (2009) Synthesis, structural characterization, thermal and electrochemical studies of mixed ligand Cu(II) complexes containing 2-phenyl-3-(benzylamino)-1,2-dihydroquinazoline-4-(3H)-one and bidentate N-donor ligands. Spectrochem Acta Part A 74:1100–1106.  https://doi.org/10.1016/j.saa.2009.09.015 CrossRefGoogle Scholar
  36. Schiff H (1864) Mittheilungen aus dem Universitätslaboratorium in Pisa: eine neue reihe organischer Basen. Justus Liebigs Annalen der Chemie 131:118–119.  https://doi.org/10.1002/jlac.18641310113 CrossRefGoogle Scholar
  37. Sztanke K, Maziarka A, Osinka A, Sztanke M (2013) An insight into synthetic Schiff bases revealing antiproliferative activities in vitro. Bioorg Med Chem 21:2648–3666.  https://doi.org/10.1016/j.bmc.2013.04.037 Google Scholar
  38. Tian X, Schaich KM (2013) Effects of molecular structure on kinetics and dynamics of the trolox equivalent antioxidant capacity Assay with ABTS+•. J Agric Food Chem 61:5511–5519.  https://doi.org/10.1021/jf4010725 CrossRefGoogle Scholar
  39. Walker RB, Everette JD (2009) Comparative reaction rates of various antioxidants with ABTS radical cation. J Agric Food Chem 57:1156–1161.  https://doi.org/10.1021/jf8026765 CrossRefGoogle Scholar
  40. Wang XS, Sheng J, Lu L, Yang K, Li YL (2011) Combinatorial synthesis of 3-Arylidene aminoquinazolin-4(1H)-one derivatives catalyzed by iodine in ionic liquids. ACS Combinat Sci 13:196–199.  https://doi.org/10.1021/co1000713 CrossRefGoogle Scholar
  41. Zahedifard M, Faraj FL, Paydar M, Looi ChY, Hajrezaei M, Hasanpourghadi M, Kamalidehghan B, Majid NA, Ali HM, Abdulla MA (2015) Synthesis, characterization and apoptotic activity of quinazolinone Schiff base derivatives toward MCF-7 cells via intrinsic and extrinsic apoptosis pathways. Sci Rep 5(11544):1–17.  https://doi.org/10.1038/srep11544 Google Scholar
  42. Zhang J, Cheng P, Ma Y, Liu J, Miao Z, Ren D, Fan C, Liang M, Liu L (2016) An efficient nano CuO-catalyzed synthesis and biological evaluation of quinazolinone Schiff base derivatives and bis-2,3-dihydroquinazolin-4(1H)-ones as potent antibacterial agents against Streptococcus lactis. Tetrahedron Lett 57:5271–5277.  https://doi.org/10.1016/j.tetlet.2016.10.047 CrossRefGoogle Scholar
  43. Zoubi WA (2013) Biological activities of Schiff bases and their complexes: a review of recent works. Int J Org Chem 3:73–95.  https://doi.org/10.4236/ijoc.2013.33A008 CrossRefGoogle Scholar

Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2017

Authors and Affiliations

  • Zuzana Hricovíniová
    • 1
  • Michal Hricovíni
    • 2
  • Katarína Kozics
    • 3
  1. 1.Institute of ChemistrySlovak Academy of SciencesBratislavaSlovakia
  2. 2.Faculty of Chemical and Food Technology, Institute of Physical Chemistry and Chemical PhysicsSlovak University of TechnologyBratislavaSlovakia
  3. 3.Cancer Research Institute, Biomedical Research CenterSlovak Academy of SciencesBratislavaSlovakia

Personalised recommendations