Skip to main content
SpringerLink
Log in

Molecular Docking Studies, Antiproliferative Evaluation, and Synthesis of 7-(1H-Indol-3-yl)pyrido[2,3-d]pyrimidine Derivatives

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

Abstract—

A series of indolylpyridopyrimidine derivatives were designed, synthesized, and tested for their in vitro cytotoxic activity using the SRB assay method. The antiproliferative activities of the new compounds were tested against HepG-2 and MCF-7 human cancer cell lines. All candidates exhibited more powerful activity against MCF-7 with IC50 values ranging from 7.5 ± 0.5 to 10.0 ± 1.1 μM compared to the positive control, Doxorubicin. On the other hand compounds (VIIId), (Vc), and (VIIIb), had similar activities on HepG-2; the other compounds had slightly fewer activities relative to the positive control doxorubicin. The results of the molecular docking demonstrated that the biological and theoretical concepts are well-computable, adding to the research’s value. As a result, this study provides a framework for additional research towards indolylpyridopyrimidine derivatives as antiproliferative drugs.

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.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.
Fig. 7.
Fig. 8.
Fig. 9.
Fig. 10.
Fig. 11.
Fig. 12.

Similar content being viewed by others

REFERENCES

  1. Jalili, F.M. Zarei, M.A., Zolfigol, S., and Rostamnia, A.R., Microporous Mesoporous Mater., 2020, vol. 294, pp. 109865–109876. https://doi.org/10.1016/j.micromeso.2019.109865

    Article  CAS  Google Scholar 

  2. Ambati, S.R., Patel, J.L., Gudala, S.K., Chandrakar, S., Penta, S., Mahapatra, and Banerjee, S., Synth. Commun., 2020, vol. 50, pp. 104–111. https://doi.org/10.1080/00397911.2019.1686526

    Article  CAS  Google Scholar 

  3. Azzam, R.A., Elgemeie, G., and Osman, R.S., J. Mol. Struct., 2020, vol. 1201, pp. 127194–127206. https://doi.org/10.1016/j.molstruc.2019.127194-127206

    Article  CAS  Google Scholar 

  4. El-Nassan, H.B., Eur. J. Med. Chem., 201, vol. 146, pp. 2031–2036. https://doi.org/10.1016/j.ejmech.2011.02.055

  5. Toogood, P.L., Harvey, P.J., Repine, J.T., and Fry, D.W., J. Med. Chem., 2005, vol. 48, pp. 2388–2406. https://doi.org/10.1021/jm049354h

    Article  CAS  PubMed  Google Scholar 

  6. Vander Wel, S.N., Harvey, P.J., and McNamara, D.J., J. Med. Chem. 2005, vol. 48, pp. 2371–2387. https://doi.org/10.1021/jm049355+

    Article  CAS  Google Scholar 

  7. Turner, N.C., Ro, J., and Andre, F., N. Engl. J. Med., 2015, vol. 373, pp. 209–219. https://doi.org/10.1056/NEJMoa1505270

    Article  CAS  PubMed  Google Scholar 

  8. Dakhlaoui, I., Vahdati, S., Maalej, E., Chabchoub, F., Wiese, M., and Marco-Contelles, J., Bioorg. Chem., 2021, vol. 116, pp. 105326–105335. https://doi.org/10.1016/j.bioorg.2021.105326

  9. Eissa, A.A., Aljamal, K.F., Ibrahim, H.S., and Allam, H.A., Bioorg. Chem., 2021, vol. 116, pp. 105318–105328. https://doi.org/10.1016/j.bioorg.2021.105318

    Article  CAS  PubMed  Google Scholar 

  10. Cordeu, L., Cubedo, E., and Bandres, E., Bioorg. Med. Chem., 2007, vol. 15, pp. 1659–1669. https://doi.org/10.1016/j.bmc.2006.12.010

    Article  CAS  PubMed  Google Scholar 

  11. Fares, M., Abou-Seri, S.M., Abdel-Aziz, H.A., Abbas, S., Youssef, M., and Eladwy, R., Eur. J. Med. Chem., 2014, vol. 83, pp. 155–166. https://doi.org/10.1016/j.ejmech.2014.06.027

    Article  CAS  PubMed  Google Scholar 

  12. Sundberg, R.J., Indoles, San Diego: Academic Press, 1996.

    Google Scholar 

  13. Zahran, M.A. and Ibrahim, A., J. Chem. Sci., 2009, vol. 121, pp. 455–462. https://doi.org/10.1007/s12039-009-0054-3

    Article  CAS  Google Scholar 

  14. Chavan, R., More, N., and Bhosale, A.V. Trop. J. Pharm. Res., 2011, vol. 10, pp. 463–473. https://doi.org/10.4314/tjpr.v10i4.12

    Article  CAS  Google Scholar 

  15. Tian, D., Luo, G., Chen, H., Tang, X. and Liu, Y., Acta Crystallogr., Sect. E, 2011, vol. 67, article ID o1851. https://doi.org/10.1107/S1600536811024299

  16. Dilli, V., Mastan, M., and Sobha, R., IOSR J. Appl. Chem., 2012, vol. 2, pp. 44–49. ISSN: 2278–5736

  17. Kamel, M., Abdel-Hameid, M., El-Nassan, H., and El-Khouly, E., Med. Chem., 2019, vol. 15, pp. 873–882. https://doi.org/10.2174/1573406415666190408125514

    Article  CAS  PubMed  Google Scholar 

  18. Muhammad, Z.A., Radwan, M.A., Farghaly, T.A., Gaber, H.M., and Elaasser, M.M., Mini Rev. Med. Chem., 2019, vol.19, pp. 79–86. https://doi.org/10.2174/1389557518666180724094244

  19. Kumar, D., Kumar, N.M., Akamatsu, K., Kusaka, E. Harada, H. and Ito, T., Bioorg. Med. Chem. Lett., 2010, vol. 20, pp. 3916–3919. https://doi.org/10.1016/j.bmcl.2010.05.016

    Article  CAS  PubMed  Google Scholar 

  20. Wang, H. and Zeng, J., Can. J. Chem., 2009, vol. 87, pp. 1209–1212. https://doi.org/10.1139/V09-106

    Article  CAS  Google Scholar 

  21. Radwan, M.A, Al Rugaie, O., Al Abdulmonem, W., Alfaifi, M.Y., and Elbehairi, S., Arabian J. Chem., 2021, vol. 14, pp. 103209–103216. https://doi.org/10.1016/j.arabjc.2021.10320

    Article  CAS  Google Scholar 

  22. Radwan, M.A., Rugaie, O.A., Abdulmonem, W.A., Alfaifi, M.Y., and Elbehairi, S.E.I., Egypt. J. Chem., 2021, vol. 64, pp. 4697–4706. https://doi.org/10.21608/ejchem.2021.84060.4117

    Article  Google Scholar 

  23. Radwan, M.A.A., Alminderej, F.M., Tolan, H.E.M., and Awad, H.M., J. Appl. Pharm. Sci., 2020, vol. 10, pp. 12–22. https://doi.org/10.7324/JAPS.2020.10902

    Article  CAS  Google Scholar 

  24. Radwan, M.A., Alminderej, F.M., and Awad, H.M., Molecules, 2020, vol. 25, no. 2, p. 255. https://doi.org/10.3390/molecules25020255

  25. El-Nezhawy, A.O., Eweas, A.F., Radwan, M.A., and El-Naggar, T.B., J. Heterocycl. Chem. 2016, vol. 53, pp. 271–279. https://doi.org/10.1002/jhet.2422

  26. Ghorab, M., Taha, N.M., Radwan, M.A.A., Amin, N.E., Shehab, M.A., and Faker, I.M., Phosph., Sulfur, Silicon, 2008, vol. 183, pp. 2891–2905. https://doi.org/10.1080/10426500802505408

  27. Radwan, M.A. and Abbas, E., Monatsh. Chem., 2009, vol. 140, pp. 229–233. https://doi.org/10.1007/s00706-008-0061-y

    Article  CAS  Google Scholar 

  28. El Nezhawy, A., Radwan, M.A., and Gaballah, S., Arkivoc, 2009, vol. 12, pp. 119–130. https://doi.org/10.3998/ark.5550190.0010.c10

    Article  Google Scholar 

  29. Fatma, S., Singh, D., Ankit, P., Mishra, P., Singh, M., and Singh, J., Tetrahedron Lett., 2014, vol. 55, pp. 2201–2207. https://doi.org/10.1002/chin.201437160

  30. Khalaf, H.S., Tolan, H.E., Radwan, M.A., Mohamed, A.M., Awad, H.M., and El-Sayed, W.A., Nucleosides, Nucleotides, Nucleic Acids, 2020, vol. 39, pp. 1036–1056. https://doi.org/10.1080/15257770.2020.1748649

  31. Radwan, M.A., Alminderej, F.M., Tolan, H.E., and Awad, H.M., Egypt. J. Chem., 2021, vol. 64, pp. 1–9. https://doi.org/10.21608/ejchem.2020.32862.2694

  32. Khalaf, H., Tolan, H., El-Bayaa, M. Radwan, M.A., El-Manawaty, M., and El-Sayed, W., Russ. J. Gen. Chem., 2020, vol. 90, pp. 1706–1715. https://doi.org/10.1134/S1070363220090182

  33. Zayed, E.M., Zayed, M.A., Abd El Salam, H.A., and Nawwar, G.A., Appl. Organomet. Chem., 2018, vol. 32, article ID e4535. https://doi.org/10.1002/aoc.4535

    Article  CAS  Google Scholar 

  34. Zayed, E.M., Zayed, M.A., Fahim, A. M., and El-Samahy, F.A., Appl. Organomet. Chem., 2017, vol. 31, article ID e3694. https://doi.org/10.1002/aoc.3694

    Article  CAS  Google Scholar 

  35. Zayed, E. M., El-Samahy, F.A., and Mohamed, G.G, Appl. Organomet. Chem., 2019, 3 vol. 3, article ID e5065. https://doi.org/10.1002/aoc.5065

  36. Zayed, E.M., Zayed, M.A., Abd El Salam, H.A., and Noamaan, M.A, Comp. Biol. Chem., 2019, vol. 78, pp. 260–272. https://doi.org/10.1016/j.compbiolchem.2018.12.008

    Article  CAS  Google Scholar 

Download references

Funding

The authors gratefully acknowledge Qassim University represented by the Deanship of Scientific Research on the financial support for this research under the number (Cos-2019-2-2-1-5669) during the academic year 1440 AH/ 2019 AD.

Author information

Authors and Affiliations

  1. Department of Chemistry, Collage of Science, Qassim University, Buraidah, Saudi Arabia

    M. A. Radwan

  2. Applied Organic Chemistry Department, National Research Center, Dokki, Egypt

    M. A. Radwan

  3. Department of Basic Medical Sciences, Unaizah College of Medicine and Medical Sciences, Qassim University, Unaizah, Saudi Arabia

    O. Al Rugaie

  4. Department of Pathology, College of Medicine, Qassim University, Buraidah, Saudi Arabia

    W. Al Abdulmonem

  5. Tanning Materials and Leather Technology Department, National Research Centre, El-Behouth St, Dokki, Cairo, Egypt

    H. Awad

  6. Green Chemistry Department, National Research Centre, Giza, Egypt

    E. Zayed

Authors
  1. M. A. Radwan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. Al Rugaie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. Al Abdulmonem
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Awad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Zayed
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. A. Radwan.

Ethics declarations

COMPLIANCE WITH ETHICAL STANDARDS

This article does not contain any studies involving human participants performed by any of the authors and does not contain any studies involving animals performed by any of the authors.

Conflict of Interests

The authors declare that they have no conflicts of interests.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Radwan, M.A., Al Rugaie, O., Al Abdulmonem, W. et al. Molecular Docking Studies, Antiproliferative Evaluation, and Synthesis of 7-(1H-Indol-3-yl)pyrido[2,3-d]pyrimidine Derivatives. Russ J Bioorg Chem 48, 809–820 (2022). https://doi.org/10.1134/S1068162022040161

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162022040161

Keywords:

Search

Navigation