Naufal Ma’arif, Anissa Nofita Sari, Wirdatun Nafisah, Annisa Krama, Hanum Isfaeni, Rusdi Rusdi, Gusnia M. Gholam
Triple-negative breast cancer (TNBC) represents a highly aggressive form of breast cancer, and the treatment options available are regarded as particularly challenging. The lack of specific molecular targets, including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), accounts for this situation. This study investigates the molecular interactions between natural compounds derived from Stylissa carteri and Epidermal Growth Factor Receptor (EGFR) and RAF proteins, which are promising targets for therapeutic strategies in triple-negative breast cancer (TNBC), utilizing in silico techniques. Nine compounds derived from Stylissa carteri were obtained from the Knapsack and PubChem servers. These compounds' biological activities and interactions with EGFR and RAF proteins were analyzed. The findings indicated that the nine compounds exhibited various biological activities inhibiting TNBC. Docking and molecular dynamics analysis revealed that stevensine and dibutyl phthalate exhibited the highest binding affinity and the most stable interactions with the EGFR-RAF protein complex. Docking analysis revealed binding affinity values between −5.4 and −7.9 kcal/mol. The most robust binding interaction was noted for (Z)-hymenialdisine with RAF (−7.9 kcal/mol), whereas 1,2-benzenediol exhibited the weakest interaction (−5.7 kcal/mol). Dibutyl phthalate exhibited the highest binding affinity for EGFR, measured at −7.0 kcal/mol. The findings indicate that compounds derived from Stylissa carteri exhibit potential efficacy in targeting EGFR and RAF in triple-negative breast cancer (TNBC). © 2025 Ma’arif et al.
Biology Education Department, Faculty of Mathematics and Natural Science, Universitas Negeri Jakarta, East Jakarta, 13320, Indonesia; Bioinformatics Research Center, INBIO Indonesia, Malang, 65162, Indonesia; Magister Biology Program, Faculty of Mathematics and Natural Science+6, Universitas Brawijaya, Malang, 65145, Indonesia; Research Center of Vaccine and Drug, Research Organization for Health, National Research and Innovation Agency (BRIN), Bogor, 16911, Indonesia; Biology Department, Faculty of Mathematics and Natural Science, Universitas Negeri Surabaya, Surabaya, 60231, Indonesia; Tsukuba-Plant Innovation Research Center, Institute of Life and Environmental Sciences, University of Tsukuba, Ibaraki, 305-8572, Japan; Departement of Biochemistry, Faculty of Mathematics and Natural Sciences, Bogor Agricultural University, Bogor, 16680, Indonesia
