Exploring Structural Requirement of Curcumin-Based CK2 Inhibitors as Anticancer Agents: 3D-QSAR, Pharmacophore Modeling, Virtual Screening, and Molecular Docking.

Abstract

Introduction: Casein Kinase 2 (CK2), discovered as one of the earliest protein kinases, is a ubiquitous Ser/Thr protein kinase-specific to acidic environments. CK2 has been implicated in regulating diverse cellular processes and has been linked to the onset of various diseases, including cancer.

Method: Consequently, modulating CK2 function has emerged as a potential therapeutic strategy. However, currently, available CK2 inhibitors or modulators often lack sufficient specificity and potency.

Results: The results were validated through QSAR of curcumin derivatives, Pharmacophore modeling, virtual screening performed for filtered curcumin-like featured derivatives from the database, and Molecular Docking approaches. Since there is a solved crystal structure of high-resolution Xray crystal structures of Human protein kinase CK2 alpha in complex with ferulic aldehyde.

Conclusion: Also, structure-based virtual screening was performed against a total of 3253 compounds from different libraries, and only the top 4 best-hit compounds with exceptional docking scores exceeding >-7 kcal/mol (more than 7 kcal/mol) were screened and analyzed. However, to validate their therapeutic potential, these compounds require in-vitro evaluation to assess their CK2 targeting ability.