Design and synthesis of sulphonyl acetamide analogues of quinazoline as anticancer agents

Abstract

A series of sulphonyl acetamide analogues were generated on the quinazoline ring through a multistep reaction starting from 2-mercapto-3H-quinazolin-4-one. The library of synthesised analogues was screened for in vitro cytotoxic activity against various human cancer cell lines such as HCT-1 and HT-15 (colon), MCF-7(Breast), PC-3 (Prostrate), SF268 (CNS) using MTT method. From the bioassay results, it was observed that even though most of the synthesised derivatives exhibited a good potency against various screened cancer cell lines, but compound 10d, 10k, and 10n were found to show very potent anticancer activity on all tested cancer cell lines with compound 10d showing IC50 value of 0.08, 0.3 and 0.55 µM on HT-29, MCF-7 and PC-3 cell lines, respectively, compound 10k showing IC50 value of 0.12, 0.03 and 0.08 µM on HCT-15, HT-29 and PC-3 cell lines, respectively, and compound 10n showing IC50 values of 0.1, 0.34, 0.52 and 0.26 on HCT-15, HT-29, MCF-7 and PC-3 cell lines, respectively.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Scheme 1

References

  1. Ahmad I (2017) An insight into the therapeutic potential of quinazoline derivatives as anticancer agents. MedChemComm 8(5):871–885

    Article  Google Scholar 

  2. Alaa A-M, Abou-Zeid LA, El Tahir KEH, Mohamed MA, El-Enin MAA, El-Azab AS (2016) Design, synthesis of 2, 3-disubstitued 4 (3H)-quinazolinone derivatives as anti-inflammatory and analgesic agents: COX-1/2 inhibitory activities and molecular docking studies. Bioorg Med Chem 24(16):3818–3828

    Article  Google Scholar 

  3. Al-Rashood ST, Aboldahab IA, Nagi MN, Abouzeid LA, Abdel-Aziz AA, Abdel-hamide SG et al. (2006) Synthesis, dihydrofolate reductase inhibition, antitumor testing, and molecular modeling study of some new 4(3H)-quinazolinone analogs. Bioorg Med Chem 14(24):8608–8621

    CAS  Article  Google Scholar 

  4. Atul T (2016) A study on biological importance of nitrogenous based heterocyclic compounds. Int J Theort Appl Sci 8(1):53–54

    Google Scholar 

  5. Bhattacharjee AK, Hartell MG, Nichols DA, Hicks RP, Stanton B, Van Hamont JE et al. (2004) Structure activity relationship study of antimalarial indolo [2, 1-b] quinazoline-6, 12-diones (tryptanthrins). Three dimensional pharmacophore modeling and identification of new antimalarial candidates. Eur J Med Chem 39(1):59–67

    CAS  Article  Google Scholar 

  6. Christiana C (2017) MPH. What you need to know about chemotherapy. https://www.medicalnewstoday.com/articles/158401.php

  7. Cruz-Lopez O, Conejo-García A, Nunez MC, Kimatrai M, Garcia-Rubino ME, Morales F et al. (2011) Novel substituted quinazolines for potent EGFR tyrosine kinase inhibitors. Curr Med Chem 18(7):943–963

    CAS  Article  Google Scholar 

  8. Davoll J, Johnson AM (1970) Quinazoline analogues of folic acid. J Chem Soc 8:997–1002

    CAS  Google Scholar 

  9. Dempcy RO, Skibo EB (1991) Rational design of quinazoline-based irreversible inhibitors of human erythrocyte purine nucleoside phosphorylase. Biochemistry 30:8480–8487

    CAS  Article  Google Scholar 

  10. Giovanni M, Adriano G, Adriana C (2012) Quinazoline derivatives as potential anticancer agents: a patent review (2007–2010). Expert Opin Ther Pat 22 (3):223–252

    Article  Google Scholar 

  11. Kamal A, Bharathi EV, Reddy JS, Ramaiah MJ, Dastagiri D, Reddy MK et al. (2011) Synthesis and biological evaluation of 3,5-diaryl isoxazoline/isoxazole linked 2,3-dihydro quinazolinone hybrids as anticancer agents. Eur J Med Chem 46(2):691–703

    CAS  Article  Google Scholar 

  12. Kamal A, Reddy BS, Sridevi B, Ravikumar A, Venkateswarlu A, Sravanthi G et al. (2015) Synthesis and biological evaluation of phaitanthrin congeners as anti-mycobacterial agents. Bioorg Med Chem Lett 25(18):3867–3872

    CAS  Article  Google Scholar 

  13. Kamal A, Shaik TB, Malik MS (2015) Embracing synthetic lethality of novel anticancer therapies. Exp Opin Drug Discov 10:1119–1132

    Article  Google Scholar 

  14. Khazir J, Hyder I, Gayatri JL, Gayatri LP, Yandrati LP, Nalla N, Chashoo G, Mahajan A, Saxena AK, Alam MS, Qazi GN, Kumar HMS (2014) Design and synthesis of novel 1,2,3-triazole derivatives of coronopilin as anti-cancer compounds. Eur J Med Chem 82:255–262

    CAS  Article  Google Scholar 

  15. Khazir J, Singh PP, Reddy DM, Hyder I, Shafi S, Sawant SD, Chashoo G, Mahajan A, Alam MS, Saxena AK, Aravinda S, Gupta BD, Kumar HMS (2013) Synthesis and anticancer activity of novel spiro-isoxazoline and spiro-isoxazolidine derivatives of α-santonin. Eur J Med Chem 83:279–289

    Article  Google Scholar 

  16. Manuel A, Vilaboa N, Gutierrez BS, Lambea J, Tres A, Valladares M, Fernández ÁG (2011) Assessment of the evolution of cancer treatment therapies. Cancers 3:3279

    Article  Google Scholar 

  17. Martin GJ, Moss J, Avakian S (1947) Folic acid activity of N-(4-(4-quinazoline)-benzoyl) glutamic acid. J Biol Chem 167:737

    CAS  PubMed  Google Scholar 

  18. Matthews TP, Jones AM, Collins I (2013) Structure-based design, discovery and development of checkpoint kinase inhibitors as potential anticancer therapies. Expert Opin Drug Discov 8(6):621–640

    CAS  Article  Google Scholar 

  19. Moulder SL, Yakes FM, Muthuswamy SK et al. (2001) Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. Cancer Res 61:8887–8895

    CAS  PubMed  Google Scholar 

  20. Mulla AI (2017) A review: biological importance of heterocyclic compounds. Der Pharma Chem 9:141

    Google Scholar 

  21. Oatis Jr JE, Hynes JB (1977) Synthesis of quinazoline analogues of folic acid modified at position 10. J Med Chem 20:1393–1396

    CAS  Article  Google Scholar 

  22. Pragi A, Arora V, Lamba HS, Wadhwa D (2012) Importance of heterocyclic chemistry: a review. IJPSR 3:2947

    Google Scholar 

  23. Ryu CK, Kim YH, Im HA, Kim JY, Yoon JH, Kim A (2012) Synthesis and antifungal activity of 6, 7 bis(arylthio)-quinazoline-5,8-diones and furo[2, 3f]quinazolin-5-ols. Bioorg Med Chem Lett 22 (1):500–503

    Article  Google Scholar 

  24. Saurav K, Garima M, Pradeep S, Jha KK, Khosa RL, Gupta SK (2011) Quinazoline-4-one a highly important hetrocycle with diverse biological activities. Der Chem Sin 2/4:36–58

    Google Scholar 

  25. Scanlon KJ, Moroson BA, Bertino JR, Hynes JB (1979) Quinazoline analogues of folic acid as inhibitors of thymidylate synthetase from bacterial and mammalian sources. Mol Pharmacol 16:261–269

    CAS  PubMed  Google Scholar 

  26. Skelton LA, Ormerod MG, Titley J et al. (1999) A novel class of lipophilic quinazoline-based folic acid analogues: cytotoxic agents with a folate-independent locus. Br J Cancer 79:1692–1701

    CAS  Article  Google Scholar 

  27. Taliani S, Pugliesi I, Barresi E, Salerno S, Marchand C, Agama K et al. (2013) Phenylpyrazolo[1,5a]quinazolin-5(4H)-one: a suitable scaffold for the development of noncamptothecin topoisomerase I (Top1) inhibitors. J Med Chem 56(18):7458–7462

    CAS  Article  Google Scholar 

  28. Tiwary BK, Pradhan K, Nanda AK, Chakraborty R (2015) Implication of quinazoline-4 (3H)-ones in medicinal chemistry: a brief review. J Chem Biol Ther 1:104

    Google Scholar 

  29. Wang Z, Wang M, Yao X, Li Y, Tan J, Wang L et al. (2012) Design, synthesis and antiviral activity of novel quinazolinones. Eur J Med Chem 53:275–282

    CAS  Article  Google Scholar 

  30. Zahedifard M, Faraj FL, Paydar M, Yeng LC, Hajrezaei M, Hasanpourghadi M et al. (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

    Article  Google Scholar 

Download references

Acknowledgements

Authors thank University of Pretoria for providing postdoctoral fellowship to JK. We also thank Department of Biotechnology, Govt. of India, New Delhi for Providing Energy Bioscience Overseas Fellowship to BAM.

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Jabeena Khazir or Bilal Ahmad Mir or Gousia Chashoo.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Khazir, J., Mir, B.A., Pandita, M. et al. Design and synthesis of sulphonyl acetamide analogues of quinazoline as anticancer agents. Med Chem Res 29, 916–925 (2020). https://doi.org/10.1007/s00044-020-02533-4

Download citation

Keywords

  • Quinazoline
  • Anticancer
  • Sulphonyl
  • Acetamide
  • Derivatives