Molecular Docking Simulation Studies of Curcumin and Its Derivatives as Cyclin-Dependent Kinase 2 Inhibitors

Abstract

Objectives: CDK2 is a protein that plays a role in regulating the cell cycle where its overexpression contributes to uncontrolled cell proliferation. Inhibition of CDK2 has been known to be one of the mechanisms of various anticancer drugs. Curcumin is an active compound of Curcuma Longa which have been reported to inhibit the activity of Cyclin D, Cyclin E, CDK2, CDK4, and CDK6. Material and Methods:This study aims to design more active curcumin derivatives as anticancer drugs by targeting CDK2 through a molecular modelling approach. In brief, the process consist of receptor and ligand preparation, method validation, pharmacophore modelling, and docking simulation. Results:The results of molecular docking simulation show that the free bonding energy (∆G) of curcumin and kurkumod 23 and 24 (the best modification of curcumin) are -7.80, -9.15, and -9.36 kcal/mol respectively. The hydrogen interaction between kurkumod 23 and 24 with CDK occurred on Lys33 residue which is considered as a potential interaction side for CDK2 inhibitor compounds. Pharmacophore modelling showed that kurkumod 23 and 24 have a pharmacophore-fit value of 45.20% and 47.26% respectively. Conclusion:Based on the study result, it can be considered that kurkumod 23 and 24 are the best and most potential modifications of curcumin as CDK-2 antagonist, which is based on the interactions that occur between these two derivatives with amino acid residues from the CDK2 receptor.

Cinnamamide-chalcone derivatives as CDK2 inhibitors: synthesis, pharmacological evaluation, and molecular modelling study

“…The pi-pi stacking with Phe80 seems to be an important but not a compulsory interaction for the compounds to be active as it was not observed in case of all compounds. The interactions observed in this study are consistent with some of the other reported studies [13,32,[33][34][35][36][37].…”

In vitro Evaluation and Molecular Docking Analysis of Potential Anticancer Compounds from Syzygium alternifolium

“…Apigenine, Kaempferol and Quercitin have demonstrated remarkable binding affinity towards Cyclin-dependent kinase-2. Apigenine shown highest docking score -9.8 in comparison to other compound topwards CDK-2 [17]. Quercetin, Kaemferol and Apigenine have demonstrated remarkable binding affinity towards TOPO-2.…”

Synthesis and Evaluation of Some New 4H-Pyran Derivatives as Antioxidant, Antibacterial and Anti-HCT-116 Cells of CRC, with Molecular Docking, Antiproliferative, Apoptotic and ADME Investigations

“…The Glide module [ 88 ] in extra precision (XP) mode [ 89 ] was used for flexible molecular docking of all the molecules inside the active site (ATP binding site of the kinase) [ 90 ], using default settings, as recommended in the manual for the Glide module from Schrodinger. The residues Lys33, Glu51 and Asp145, constituting the active site, were set as flexible residues.…”