Exploring ISecurigera securidaca/I Seeds as a Source of Potential CDK1 Inhibitors: Identification of Hippeastrine and Naringenin as Promising Hit Candidates

CDK1 (cyclin dependent kinase 1) is a key regulator of the cell cycle and is frequently dysregulated in cancer, making it a promising target for anticancer therapy. Securigera securidaca L. (S. securidaca) seeds, traditionally used in folk medicine for various ailments including cancer, were examined for their potential as CDK1/Cks2 inhibitors using in silico approaches. A total of 14 phytocompounds was identified in the GC/MS chromatogram, with gingerone being the most abundant at 25.67% and hippeastrine the least at 2%. Major constituents of the essential extract, including gingerol, eugenol, α-curcumene, and gingerol, showed high values and made up 52% of the total content of the volatile extract. Molecular docking and ADMET studies suggested that hippeastrine and naringenin are potential hit candidates against CDK1, exhibiting good drug-like properties and molecular interactions with desirable pharmacokinetic and toxicological characteristics close to dinaciclib. Furthermore, molecular dynamics (MD) simulations showed that both compounds exhibited stable conformations inside the binding site over the 100 ns MD simulation, suggesting they may stabilize the protein structure by reducing the flexibility of the CDK1 backbone. Additionally, MM-PBSA calculations further supported the stability of hippeastrine and naringenin in CDK1 complexes. Overall, these findings suggest that hippeastrine and naringenin are potential hit candidates for CDK1 inhibition, providing valuable insight into their binding and stability within the active site of CDK1. Further investigation of these compounds with in vitro and in vivo assays is warranted to assess their potential as CDK1 inhibitors for cancer therapy.