Flavonoids as Dual Inhibitors of MELK and LYN Kinases in Cervical Cancer: An In Silico Molecular Docking Analysis.

Abstract

Introduction: Cervical cancer (CC) is among the most prevalent cancers affecting women globally, with a substantial number of deaths reported annually. Despite advancements in treatment, the persistently high mortality rate underscores the urgent need for novel and effective therapeutic strategies.

Methods: This study screened a library of 240 flavonoids against maternal embryonic leucine zipper kinase (MELK) and LYN using molecular docking methods to achieve precise calculations. These proteins play critical roles in CC progression, and their simultaneous inhibition could mark a significant step forward in multitargeted drug design.

Results: Molecular docking revealed binding affinities ranging from -10.0649 to -8.14296 kcal/mol for MELK and -10.2748 to -8.5237 kcal/mol for LYN. The screening process was complemented by pharmacokinetics and interaction fingerprinting analyses, which confirmed that the flavonoids effectively bound to optimal sites, forming stable complexes through multiple interactions. Molecular dynamics simulations extended to 100 ns further validated the stability of these protein-ligand complexes.

Discussion: The findings indicate that the top-ranked compounds exhibit strong binding affinities and stable interactions, highlighting their potential as multitargeted therapeutic agents against CC.

Conclusion: These findings set the stage for future experimental and clinical studies to validate our results and facilitate the development of novel, flavonoid-based therapeutic strategies against cervical cancer, potentially revolutionizing the treatment landscape of this disease.