Assessing the Anticancer Potential of Compounds from <i>Caesalpinia sappan</i> Wood against Mutant EGFR in Lung Squamous Cell Carcinoma: Computational Insights

Background Lung squamous cell carcinoma (LUSC), a subtype of non-small cell lung cancer (NSCLC), frequently harbors mutations in the epidermal growth factor receptor (EGFR), which regulates cell proliferation and survival. This makes EGFR an attractive therapeutic target for LUSC. Advances in computational drug discovery have facilitated the identification of natural compounds with anticancer potential. Caesalpinia sappan, a medicinal plant with known therapeutic properties, contains bioactive phytochemicals that may exhibit anticancer effects. Objectives The purpose of the study is to assess the anticancer potential of phytochemicals from C. sappan against mutant EGFR in LUSC through computational approach, including molecular docking and biological activity prediction. Materials and Methods Thirty phytochemicals from C. sappan were retrieved from the Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) database. Drug-likeness was assessed using Lipinski’s rule of five, and ADMET properties were evaluated using the SwissADME web server. Compounds permeable to the blood-brain barrier (BBB) were excluded to mitigate central nervous system (CNS)-related side effects, resulting in the selection of 10 compounds for molecular docking with mutant EGFR using PyRx software. Docking scores were compared with doxorubicin, a standard anticancer drug. Biological activity prediction was performed using the PASS web server. Results Of the 30 phytochemicals screened, 24 adhered to Lipinski’s rule of five, and 14 were excluded due to BBB permeability. Molecular docking revealed that nine compounds had significant binding affinity toward mutant EGFR, with binding energies comparable to doxorubicin. Among these, norvaline exhibited the lowest binding affinity (–4.8 kcal/mol). Biological activity prediction indicated that eight of the nine lead compounds displayed antineoplastic activity, with oleic acid being the exception. Conclusion This study identified several phytochemicals from C. sappan with the potential to inhibit mutant EGFR in LUSC. The exclusion of BBB-permeant compounds enhances the clinical relevance of these findings by minimizing CNS-related side effects. These results underscore the promise of natural compounds as alternative therapeutic agents for targeting EGFR in LUSC and warrant further in vitro and in vivo validation.