Skip to content
2000
image of Design, Synthesis, and Biological Evaluation of Triazine-4-Thiazolidinone Hybrid Molecules as Modulator of Breast Cancer

Abstract

Introduction/Objective

Breast cancer is the most prevalent cancer among women globally, characterized by the uncontrolled growth of breast cells, and remains a leading cause of cancer-related morbidity and mortality. It can occur in both men and women, though it is significantly rarer in men. The multifactorial nature of breast cancer involves genetic mutations, hormonal influences, and complex cellular signalling pathways. The disease is typically classified into different subtypes based on hormone receptor status, which influences treatment decisions. Early detection through regular screening, such as mammograms, and awareness of symptoms significantly improve prognosis. Treatment options vary based on the stage and type of breast cancer and may include surgery, radiation therapy, chemotherapy, hormone therapy, and targeted therapy. We aimed to design novel compounds based on reported active pharmacophoric features and validate them through molecular modelling. These designed compounds were then synthesized and characterized. Finally, a biological evaluation of the synthesized compounds was performed to assess their efficacy.

Methods

Thirty compounds were designed based on a literature survey. Out of these compounds, twelve compounds were found good on the docking studies, and these twelve new derivatives (RD 01-12) were synthesized and subjected to (EGFR assay), and ADMET profiling to identify the most potent compound.

Results

All 12 compounds were synthesised and characterised. Out of 12 compounds, RD-09 emerged as the most potent enzymatic assay with an IC value of 1.21 ± 0.03 µM, confirmed by docking studies; it possessed a docking score of -7.302 against the EGFR receptor. These compounds were further characterized using IR, 1H NMR, and mass spectrometry.

Conclusion

Based on pharmacophoric features, twelve triazine-4-thiazolidinone derivatives (RD 01-12) were designed, synthesized, and evaluated for their potential as EGFR-2 inhibitors, specifically targeting triple-negative breast cancer (TNBC). Among 12 synthesised compounds, compound RD-09 demonstrated the most significant activity with an IC value of 1.21 ± 0.03 µM. Docking studies further supported its binding interaction with the catalytic domain of the EGFR receptor. The combined results from , and ADMET profiling suggest that RD-09 holds promise as a leading compound for further development in the treatment of TNBC.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cei/10.2174/0115734080343685250121045944
2025-02-24
2025-09-26

  • From This Site

    /content/journals/cei/10.2174/0115734080343685250121045944
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Abdu-Allah H.H.M. Abdel-Moty S.G. El-Awady R. El-Shorbagi A.N.A. Design and synthesis of novel 5-aminosalicylate (5-ASA)–4-thiazolinone hybrid derivatives with promising antiproliferative activity. Bioorg. Med. Chem. Lett. 2016 26 7 1647 1650 10.1016/j.bmcl.2016.02.073 26947606
    [Google Scholar]
  2. Abu Samaan T.M. Samec M. Liskova A. Kubatka P. Büsselberg D. Paclitaxel’s mechanistic and clinical effects on breast cancer. Biomolecules 2019 9 12 789 10.3390/biom9120789 31783552
    [Google Scholar]
  3. Arnold M. Morgan E. Rumgay H. Current and future burden of breast cancer: Global statistics for 2020 and 2040. Breast 2022 66 15 23 10.1016/j.breast.2022.08.010 36084384
    [Google Scholar]
  4. Parkin D.M. Global cancer statistics in the year 2000. Lancet Oncol. 2001 2 9 533 543 10.1016/S1470‑2045(01)00486‑7 11905707
    [Google Scholar]
  5. Han S.A. Kim S.W. BRCA and breast cancer-related high-penetrance genes. Adv. Exp. Med. Biol. 2021 1187 473 490 10.1007/978‑981‑32‑9620‑6_25 33983595
    [Google Scholar]
  6. Smolarz B. Nowak A.Z. Romanowicz H. Review of literature. Cancers 2022 14 10 2569 10.3390/cancers14102569 35626173
    [Google Scholar]
  7. Mavaddat N. Dorling L. Carvalho S. Pathology of tumors associated with pathogenic germline variants in 9 breast cancer susceptibility genes. JAMA Oncol. 2022 8 3 e216744 10.1001/jamaoncol.2021.6744 35084436
    [Google Scholar]
  8. Laborda-Illanes A. Sanchez-Alcoholado L. Dominguez-Recio M.E. Breast and gut microbiota action mechanisms in breast cancer pathogenesis and treatment. Cancers 2020 12 9 2465 10.3390/cancers12092465 32878124
    [Google Scholar]
  9. Li Z. Wei H. Li S. Wu P. Mao X. The role of progesterone receptors in breast cancer. Drug Des. Devel. Ther. 2022 16 305 314 10.2147/DDDT.S336643 35115765
    [Google Scholar]
  10. Paplomata E. O’Regan R. The PI3K/AKT/mTOR pathway in breast cancer: Targets, trials and biomarkers. Ther. Adv. Med. Oncol. 2014 6 4 154 166 10.1177/1758834014530023 25057302
    [Google Scholar]
  11. De Luca A. Maiello M.R. D’Alessio A. Pergameno M. Normanno N. The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: Role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin. Ther. Targets 2012 16 S17 S27 10.1517/14728222.2011.639361 22443084
    [Google Scholar]
  12. Barriga V. Kuol N. Nurgali K. Apostolopoulos V. The complex interaction between the tumor micro-environment and immune checkpoints in breast cancer. Cancers 2019 11 8 1205 10.3390/cancers11081205 31430935
    [Google Scholar]
  13. Masuda H. Zhang D. Bartholomeusz C. Doihara H. Hortobagyi G.N. Ueno N.T. Role of epidermal growth factor receptor in breast cancer. Breast Cancer Res. Treat. 2012 136 2 331 345 10.1007/s10549‑012‑2289‑9 23073759
    [Google Scholar]
  14. Thike A.A. Cheok P.Y. Jara-Lazaro A.R. Tan B. Tan P. Tan P.H. Triple-negative breast cancer: Clinicopathological characteristics and relationship with basal-like breast cancer. Mod Pathol. An Offi J Unit Stat Canad Acad Patholo 2010 23 1 123 133
    [Google Scholar]
  15. Downward J. Yarden Y. Mayes E. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 1984 307 5951 521 527 10.1038/307521a0 6320011
    [Google Scholar]
  16. Qiu C. Tarrant M.K. Boronina T. In vitro enzymatic characterization of near full length EGFR in activated and inhibited states. Biochemistry 2009 48 28 6624 6632 10.1021/bi900755n 19518076
    [Google Scholar]
  17. Ayaz M Alam A Biooriented synthesis of ibuprofen-clubbed novel bis -schiff base derivatives as potential hits for malignant glioma: In vitro anticancer activity and in silico approach. ACS Omega 2023 8 51 49228 49243 10.1021/acsomega.3c07216 38173864
    [Google Scholar]
/content/journals/cei/10.2174/0115734080343685250121045944
Loading
Design, Synthesis, and Biological Evaluation of Triazine-4-Thiazolidinone Hybrid Molecules as Modulator of Breast Cancer
Bentham Science Publishers ; https://doi.org/10.2174/0115734080343685250121045944
/content/journals/cei/10.2174/0115734080343685250121045944
/content/journals/cei/10.2174/0115734080343685250121045944
Loading

Data & Media loading...

Supplements

file format download Download

  • Article Type:     Research Article
Keywords: biological evaluation ; Breast cancer ; EGFR ; triazine ; thiazolidine-4-one hybrid

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test