Network pharmacology and molecular docking-based insights into the anti-melanoma potential of dalbergin

Of all the skin malignancies, melanoma is the most invasive and challenging to treat. Melanoma patients have a poor prognosis and a high recurrence rate despite advancements in treatment. There is substantial evidence that plant-derived bioactives prevent and treat melanoma effectively. The naturally occurring bioactive compound dalbergin, found in certain species of the Dalbergia genus, such as Dalbergia sissoo, is a neoflavanoid that has been studied for its various biological and pharmacological properties, including its anticancer activity. Nevertheless, it is uncertain what mechanism underpins its anti-melanoma therapeutic benefits. This study aims to predict potential target proteins and suggest a possible molecular mechanism for dalbergin against melanoma using multiple systems biology databases and tools. Melanoma targets were identified through online databases and compared to proteins that were anticipated to be affected by dalbergin. Furthermore, pathways such as the MAPK signalling pathway, signal transduction, transcriptional control, and apoptosis regulation were identified using KEGG pathway analysis. Cytoscape was used to build a protein-protein interaction network, and six melanoma-associated hub targets, ERK1, ERK2, MAPK14, PTPN11, CDKN1B, and DUSP6, were identified through network analysis. Molecular docking studies demonstrated strong binding between dalbergin and the selected target proteins, with ERK1 showing the best binding (- 9.7 kcal/mol). Molecular dynamics simulations were performed for over 100 ns after molecular docking to confirm the structural stability of the dalbergin and ERK1/ERK2 complexes. This indicates the rationale for dalbergin as a potential bioactive in melanoma treatment. However, these predictions require confirmation through relevant in vitro and in vivo experimental studies to verify the precise mechanism, which is a limitation of the present work and a future scope.

The online version contains supplementary material available at 10.1007/s40203-026-00604-9.