2. Academic Validation
  3. Click synthesis of some novel benzo[ d]thiazole-1,2,3-triazole hybrid compounds with benzamide and/or benzoate tethers as EGFR-dependent signaling inhibitors against breast cancer

Click synthesis of some novel benzo[ d]thiazole-1,2,3-triazole hybrid compounds with benzamide and/or benzoate tethers as EGFR-dependent signaling inhibitors against breast cancer

  • RSC Med Chem. 2025 Sep 2. doi: 10.1039/d5md00662g.
Mosa Alsehli 1,  Mohamed S Nafie 2 3 4,  Nader R Albujuq 5,  Sanaa Bardaweel 6,  Ateyatallah Aljuhani 1,  Haytham O Tawfik 7,  Shaya Yahya Alraqa 1,  Mohamed K Diab 8,  Nadjet Rezki 1,  Mohamed Reda Aouad 1
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Science, Taibah University Al-Madinah Al-Munawarah 41477 Saudi Arabia mosa_alsehli@hotmail.com ateyatallah@hotmail.com shaya97@hotmail.com nrezki@taibahu.edu.sa maouad@taibahu.edu.sa.
  • 2 Department of Chemistry, College of Sciences, University of Sharjah Sharjah P.O. 27272 United Arab Emirates (UAE) mohamed.elsayed@sharjah.ac.ae.
  • 3 Bioinformatics and Functional Genomics Research Group, Research Institute of Sciences and Engineering (RISE), University of Sharjah Sharjah 27272 United Arab Emirates.
  • 4 Chemistry Department, Faculty of Science, Suez Canal University P.O. 41522 Ismailia Egypt mohamed_nafie@science.suez.edu.eg.
  • 5 Department of Chemistry, School of Science, The University of Jordan Amman 11942 Jordan n.albujuq@ju.edu.jo.
  • 6 Department of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan Amman 11942 Jordan s.bardaweel@ju.edu.jo.
  • 7 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University Tanta 31527 Egypt haytham.omar.mahmoud@pharm.tanta.edu.eg.
  • 8 Pest Physiology Department, Plant Protection Research Institute, Agricultural Research Center Giza 12311 Egypt mohamed.diab_pgs@science.suez.edu.eg.
PMID: 41049790 DOI: 10.1039/d5md00662g
Abstract

The elaboration of anti-breast Cancer agents targeting EGFR represents a promising strategy in medicinal chemistry. Consequently, under optimized Cu(i)-catalyzed click synthesis, a new library of 1,4-disubstituted 1,2,3-triazole-based benzo[d]thiazole scaffold carrying benzamide and/or benzoate tethers 5a-t was designed, synthesized, and characterized by appropriate spectral techniques. They were also screened for their in vitro anti-cancer activity against a panel of Cancer cell lines, breast (T47D), prostate (PC3), lung (A549), and colon (HCT116) human Cancer, along with normal fibroblast cells. Notably, the hybrid triazoles, 5p, 5s, and 5t emerged as the most potent candidates, especially against T47D, with IC50 values of 15, 26, and 28 μM, respectively. Compound 5p significantly induced Apoptosis in T47D by 27.3-fold, causing total Apoptosis of 19.39% compared to 0.71%, arresting cell proliferation at the G2/M phase. Regarding EGFR as the molecular target, among the tested compounds, 5p significantly inhibited EGFR by 96.8%, with an IC50 value of 65.6 nM, compared to erlotinib, having an IC50 value of 84.1 nM. Compound 5p showed promising PI3K/Akt/mTOR inhibition as the EGFR-dependent signaling pathway with IC50 values of 4.98 μM, 0.21 μM, and 0.49 nM, respectively, compared to their reference inhibitors. Finally, a molecular docking study highlighted the binding mode disposition and binding interactions with key Amino acids as a promising EGFR Inhibitor.

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