Skip to main content
SpringerLink
Log in

Synthesis, In Vitro Antiproliferative Activity, and In Silico Studies of New Anilinoquinazoline Derivatives as Potential AntitumorAgents

  • Published:
Russian Journal of General Chemistry Aims and scope Submit manuscript

Abstract

A series of anilinoquinazoline derivatives with modification on the 2nd carbon of the aniline ring has been synthesized and characterized. The compounds have been tested for their in vitro antiproliferative activity against three NSCLC cell lines, including A549, H1650 and H1975. One of the products has demonstrated the highest IC50 value against A549 (17.60 ± 1.70 µM), surpassing the standard drug, gefitinib (34.32 ± 1.30 µM), another one has exhibited IC50 value against H1975 (9.75 ± 1.06 µM), surpassing gefitinib (31.12 ± 0.38 µM). The best performing derivatives in the antiproliferative assay have been selected for further in silico study for investigating their plausible binding mode in different EGFR kinases through molecular docking and molecular dynamics simulations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Scheme 1.
Fig. 2.

Similar content being viewed by others

REFERENCES

  1. Raghavendra, N.M., Thampi, P., Gurubasavarajaswamy, P.M., and Sriram, D., Chem. Pharm. Bull., 2007, vol. 55, p. 1615. https://doi.org/10.1248/cpb.55.1615

  2. Manivannan, E. and Chaturvedi, S.C., Bioorg. Med. Chem., 2011, vol. 19, p. 4520. https://doi.org/10.1016/j.bmc.2011.06.019

  3. Georgey, H., Abdel-Gawad, N., and Abbas, S., Molecules, 2008, vol. 13, p. 2557. https://doi.org/10.3390/molecules13102557

  4. Stamos, J., Sliwkowski, M.X., and Eigenbrot, C., J. Biol. Chem., 2002, vol. 277, p. 46265. https://doi.org/10.1074/jbc.M207135200

  5. Yun, C.H., Boggon, T.J., Li, Y., Woo, M.S., Greulich, H., Meyerson, M., and Eck, M.J., Cancer Cell, 2007, vol. 11, p. 217. https://doi.org/10.1016/j.ccr.2006.12.017

  6. Yang, Z., Gu, J.-M., Ma, Q.-Y., Xue, N., Shi, X.-W., Wang, L., Zhang, K., Wang, Y.-B., Cao, D.-Y., Guo, R., and Xing, R.-J., Future Med. Chem., 2019, vol. 11, p. 2821. https://doi.org/10.4155/fmc-2019-0220

  7. Cheng, W., Wang, S., Yang, Z., Tian, X., and Hu, Y., Drug Des. Devel. Ther., 2019, vol. 13, p. 3079. https://doi.org/10.2147/DDDT.S209481

  8. Wei, H., Duan, Y., Gou, W., Cui, J., Ning, H., Li, D., Qin, Y., Liu, Q., and Li, Y., Eur. J. Med. Chem., 2019, vol. 181, p. 111552. https://doi.org/10.1016/j.ejmech.2019.07.055

  9. Hassan, H.M.A., Denetiu, I., Khan, S.A., Rehan, M., Sakkaf, K., and Gauthaman, K., Med. Chem. Res., 2019, vol. 28, p. 1766. https://doi.org/10.1007/s00044-019-02413-6

  10. Baumann, M. and Baxendale, I.R., Beilstein J. Org. Chem., 2013, vol. 9, p. 2265. https://doi.org/10.3762/bjoc.9.265

  11. Davoodnia, A., Asian J. Chem., 2010, vol. 22, p. 1591.

  12. Ouahrouch, A., Taourirte, M., Engels, J.W., Benjelloun, S., and Lazrek, H.B., Molecules., 2014, vol. 19, p. 3638. https://doi.org/10.3390/molecules19033638

  13. Shen, C., Wang, L., Wen, M., Shen, H., Jin, J., and Zhang, P., Ind. Eng. Chem. Res., 2016, vol. 55, p. 3177. https://doi.org/10.1021/acs.iecr.5b04452

  14. Min, J., Guo, K., Suryadevara, P.K., Zhu, F., Holbrook, G., Chen, Y., Feau, C., Young, B.M., Lemoff, A., Connelly, M.C., Kastan, M.B., and Guy, R.K., J. Med. Chem., 2016, vol. 59, p. 559. https://doi.org/10.1021/acs.jmedchem.5b01092

  15. Nicholson, R.I., Gee, J.M., and Harper, M.E., Eur. J. Cancer, 2001, vol. 37, p. S9-15. https://doi.org/10.1016/s0959-8049(01)00231-3

  16. Harari, P.M., Endocr. Relat. Cancer, 2004, vol. 11, p. 689. https://doi.org/10.1677/erc.1.00600

  17. Blackledge, G. and Averbuch, S., Br. J. Cancer, 2004, vol. 90, p. 566. https://doi.org/10.1038/sj.bjc.6601550

  18. Ambrose, G.O., Afees, O.J., Nwamaka, N.C., Simon, N., Oluwaseun, A.A., Soyinka, T., Oluwaseun, A.S., and Bankole, S., Bioinformation, 2018, vol. 14, p. 241. https://doi.org/10.6026/97320630014241

  19. Tiwari, G. and Mohanty, D., PLoS One, 2013, vol. 8, p. e71340. https://doi.org/10.1371/journal.pone.0071340

  20. Nazarbahjat, N., Ariffin, A., Abdullah, Z., Abdulla, M.A., Shia, J.K.S., and Leong, K.H., Med. Chem. Res., 2016, vol. 25, p. 2015. https://doi.org/10.1007/s00044-016-1660-5

  21. Trott, O. and Olson, A.J., J. Comput. Chem., 2010, vol. 31, p. 455. https://doi.org/10.1002/jcc.21334

  22. Hanan, E.J., Baumgardner, M., Bryan, M.C., Chen, Y., Eigenbrot, C., Fan, P., Gu, X.-H., La, H., Malek, S., Purkey, H.E., Schaefer, G., Schmidt, S., Sideris, S., Yen, I., Yu, C., and Heffron, T.P., Bioorg. Med. Chem. Lett., 2016, vol. 26, p. 534. https://doi.org/10.1016/j.bmcl.2015.11.078

  23. BIOVIA, D.S., Discovery Studio Visualizer. 2016, Dassault Systèmes, San Diego.

  24. Heh, C.H., Othman, R., Buckle, M.J.C., Sharifuddin, Y., Yusof, R., and Rahman, N.A., Chem. Biol. Drug Des., 2013, vol. 82, p. 1. https://doi.org/10.1111/cbdd.12122

  25. Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., and Olson, A.J., J. Comput. Chem., 2009, vol. 30, p. 2785. https://doi.org/10.1002/jcc.21256

  26. Lim, S.K., Othman, R., Yusof, R., and Heh, C.H., Curr. Comput. Aided Drug. Des., 2017, vol. 13, p. 160. https://doi.org/10.2174/1573409912666161130122622

  27. Cousins, K.R., J. Am. Chem. Soc., 2011, vol. 133, p. 8388. https://doi.org/10.1021/ja204075s

  28. Abraham, M.J., Murtola, T., Schulz, R., Páll, S., Smith, J.C., Hess, B., and Lindahl, E., SoftwareX, 2015, vol. 1, p. 19. https://doi.org/10.1016/j.softx.2015.06.001

  29. Maier, J.A., Martinez, C., Kasavajhala, K., Wickstrom, L., Hauser, K.E., and Simmerling, C., J. Chem. Theory Comput., 2015, vol. 11, p. 3696. https://doi.org/10.1021/acs.jctc.5b00255

  30. Sousa da Silva, A.W. and Vranken, W.F., BMC Res. Notes, 2012, vol. 5, p. 367. https://doi.org/10.1186/1756-0500-5-367

  31. Wang, J., Wang, W., Kollman, P.A., and Case, D.A., J. Mol. Graph. Model., 2006, vol. 25, p. 247. https://doi.org/10.1016/j.jmgm.2005.12.005

  32. Wang, J., Wolf, R.M., Caldwell, J.W., Kollman, P.A., and Case, D.A., J. Comput. Chem., 2004, vol. 25, p. 1157. https://doi.org/10.1002/jcc.20035

  33. Jorgensen, W.L., Chandrasekhar, J., Madura, J.D., Impey, R.W., and Klein, M.L., 1983, vol. 79. https://doi.org/10.1063/1.445869

  34. Roe, D.R. and Cheatham, T.E., J. Chem. Theory Comput., 2013, vol. 9, p. 3084. https://doi.org/10.1021/ct400341p

Download references

Funding

This work was financially supported by the Ministry of Higher Education Malaysia, Fundamental Research Grant (FRGS/1/2019/SKK09/UM/02/1) and the University of Malaya Research Programme (RP035-17AFR).

Author information

Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia

    M. K. Abdulwahab & A. Ariffin

  2. Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

    R. Dzulkeflee

  3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Malaya, 50603, Kuala Lumpur, Malaysia

    T. K. Han, K. H. Leong & C. H. Heh

  4. Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

    R. A. Ruslan

Authors
  1. M. K. Abdulwahab
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Dzulkeflee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. K. Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. A. Ruslan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. H. Leong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. H. Heh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Ariffin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to K. H. Leong or A. Ariffin.

Ethics declarations

The authors declare no conflict of interest in this work.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abdulwahab, M.K., Dzulkeflee, R., Han, T.K. et al. Synthesis, In Vitro Antiproliferative Activity, and In Silico Studies of New Anilinoquinazoline Derivatives as Potential AntitumorAgents. Russ J Gen Chem 90, 2410–2418 (2020). https://doi.org/10.1134/S1070363220120294

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1070363220120294

Keywords:

Search

Navigation