2. Academic Validation
  3. Novel pyrrole-sulfonamide derivatives as EGFR inhibitors and radiosensitizers in lung cancer

Novel pyrrole-sulfonamide derivatives as EGFR inhibitors and radiosensitizers in lung cancer

  • Bioorg Chem. 2025 Nov:166:109173. doi: 10.1016/j.bioorg.2025.109173.
Mostafa G M El-Gazzar 1,  Sally S Zahran 1,  Mostafa M Ghorab 2,  Marwa G El-Gazzar 3
Affiliations

Affiliations

  • 1 Department of Drug Radiation Research, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo 11787, Egypt.
  • 2 Department of Drug Radiation Research, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo 11787, Egypt. Electronic address: [email protected].
  • 3 Department of Drug Radiation Research, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo 11787, Egypt. Electronic address: [email protected].
PMID: 41175725 DOI: 10.1016/j.bioorg.2025.109173
Abstract

Molecular hybridization strategy is of significant importance in drug discovery. This study describes the design and synthesis of sulfonamide and pyrrole hybrid in a single design as a potential epidermal growth factor enzyme (EGFR) inhibitors against non-small lung Cancer cell lines (NSCLC). All the synthesized compounds (3-11) were assessed for their in vitro cytotoxic activities against A-549 cell line and evaluated for the ability to inhibit EGFR enzyme. Compound 6 revealed the most potent cytotoxic activity (IC50 = 4.55 μM) compared to doxorubicin (IC50 = 7.52 μM) on A-549 cell line. Similarly, compound 6 exhibited a promising EGFR inhibitory activity with the lowest IC50 (0.065 μM) compared to erlotinib (IC50 0.061 μM). Compound 6 was selected to evaluate its apoptotic effect and the results showed the ability to induce early Apoptosis by 1.65 folds better than erlotinib as well as an increase in Bax/Bcl-2 ratio to 1.52 in A-549 cells. Furthermore, the effect of compound 6 on Caspase-3 was assessed and the result showed an increase in its level to 14.65 ng/mL. The synergistic effect of gamma radiation (8 Gy) was evaluated for compound 6. The effect of compound 6 was tested against EGFR L858R and EGFR T790M as well as on normal fibroblast lung (WI-38) cell line. Finally, docking study was performed within the active site of EGFR to get more insight on the binding mode of compound 6.

Keywords

Apoptosis; EGFR; Lung cancer; Molecular docking; Pyrrole; Radiosensitizer; Sulfonamide.

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