2. Academic Validation
  3. Discovery of oxazine-linked pyrimidine as an inhibitor of breast cancer growth and metastasis by abrogating NF-κB activation

Discovery of oxazine-linked pyrimidine as an inhibitor of breast cancer growth and metastasis by abrogating NF-κB activation

  • Front Oncol. 2024 Jul 29:14:1390992. doi: 10.3389/fonc.2024.1390992.
Jie Yuan 1,  Bhanuprakash C Narasimhachar 2 3,  Akshay Ravish 3,  Li Yang 4,  Hua Zhang 1,  Qun Wang 1,  Zhi Li 1,  Jun Huang 1,  Bei Wang 1,  Geng Wang 1,  Keshav Kumar Harish 5,  Arunachalam Chinnathambi 6,  Chandramohan Govindasamy 7,  Mahendra Madegowda 5,  Basappa Basappa 3
Affiliations

Affiliations

  • 1 Department of Breast, Thyroid and Vascular Surgery, Hubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
  • 2 Department of Chemistry, Yuvaraja's College, University of Mysore, Mysuru, Karnataka, India.
  • 3 Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Mysore, Karnataka, India.
  • 4 Department of Clinical Laboratory Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
  • 5 Department of Studies in Physics, University of Mysore, Mysore, India.
  • 6 Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia.
  • 7 Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
PMID: 39135991 DOI: 10.3389/fonc.2024.1390992
Abstract

Introduction: Nuclear factor kappa (NF-κB) plays a key role in Cancer cell proliferation; thus, small molecule inhibitors of NF-κB activity can effectively inhibit breast Cancer (BC) progression. We have previously reported oxazine and piperazine-linked pyrimidines as novel anti-cancer agents that can suppress NF-κB activation in BC cells. Moreover, the TRX-01 compound, an oxazine-linked pyrimidine, inhibited MCF-7 cells at a concentration of 9.17 µM in the Alamar Blue assay.

Methods: This work involved the analysis of frontier molecular orbitals, HOMO-LUMO interactions, and molecular electrostatic potential for the TRX-01 structure. Additionally, the TRX-01 compound was studied for cytotoxicity, and migration as well as invasion assays were performed on BC cells.

Results: Finally, TRX-01 blocked the translocation of NF-κB from the cytoplasm to the nucleus in MCF-7 cells and reduced NF-κB and IκBα levels in a dose-dependent manner. It also suppressed migratory and invasive properties of BC cells.

Conclusion: Overall, the data indicates that TRX-01 can function as a novel blocker of BC growth and metastasis by targeting NF-κB activation.

Keywords

NF-κB activation; TRX-01; breast cancer; cell viability and motility; heterocyclic compounds; molecular orbital analysis; nuclear factor-κB; oxazine linked pyrimidine.

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