In silico virtual screening of Citrus limetta peel phytocompounds to combat skin cancer targets: Molecular docking and molecular dynamics simulation

¹ Jaypee Institute of Information Technology, Sector-62, Noida- 201309, U.P., India Email: This email address is being protected from spambots. You need JavaScript enabled to view it.
^* Jaypee Institute of Information Technology, Sector-62, Noida- 201309, U.P., India

^* Corresponding Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

Abstract

Skin cancer is a persistent global health issue characterized by the dysregulation of critical signalling pathways. MEK1, CDK4, and IL1 have emerged as key therapeutic targets due to their roles in MAPK, CDK4, and IL1 signalling pathways. Although several existing therapies and synthetic inhibitors are available to target these proteins, their clinical use is often associated with adverse effects, highlighting the need for safer alternatives such as phytocompounds. In this study, 15 compounds identified from Citrus limetta peel extract were virtually screened against MEK1, CDK4, and IL1, using molecular docking and molecular dynamics (MD) simulation approaches. Pharmacological properties were assessed through ADMET analysis using online prediction tools. Binding affinities were evaluated and compared to the standard inhibitors, revealing that ellagic acid, hesperidin, and quercetin exhibited more favorable binding energies towards MEK1 (-10.5 kcal/mol), CDK4 (-8.8 kcal/mol), and IL1 (-7.6 kcal/mol), respectively. Further MD simulation was performed to examine the structural stability of the complexes, demonstrating stable interactions for ellagic acid-MEK1 and IL1- quercetin complexes, whereas hesperidin-CDK4 showed minor conformational changes towards the end of the simulations. The MMGBSA approach was performed to estimate binding free energies, which validated the docking results. ADMET prediction suggested acceptable drug-like properties with no significant toxicity for most compounds. Based on this study, ellagic acid, hesperidin, and quercetin show promising potential as natural alternatives to synthetic inhibitors commonly used in skin cancer treatment, effectively targeting MEK1, CDK4, and IL1. However, to confirm the therapeutic potential, further in vivo and in vitro study is needed.