Analyzing the binding affinity of anti-cancer drug sunitinib with natural and synthetic cyclodextrins: A computational study of inclusion complex formation

Hokmabady, Leila; Gholampour, Farhad; Ravari, Fatemeh

doi:10.22034/crl.2025.559567.1733

Analyzing the binding affinity of anti-cancer drug sunitinib with natural and synthetic cyclodextrins: A computational study of inclusion complex formation

Document Type : Research Article

Authors

Leila Hokmabady

Farhad Gholampour

Fatemeh Ravari

Department of Chemistry, Faculty of science, Payame Noor University (PNU), 19395-4697 Tehran, Iran

https://doi.org/10.22034/crl.2025.559567.1733

Abstract

This study delves into the potential of six different natural cyclodextrins, including alpha-cyclodextrin, beta-cyclodextrin, and gamma-cyclodextrin, and modified CDs like Amino-BCD, methylated-BCD, and 2-hydroxypropyl-beta-cyclodextrin, in Sunitinib, a potent inhibitor of multiple tyrosine kinase receptors with significant antitumor effects. Computational techniques such as molecular docking and molecular dynamics simulation were employed in this exploration. The molecular docking results reveal that Sunitinib forms inclusion complexes with all six CDs, with the highest affinity observed with methylated-beta-cyclodextrin. RMSD analysis of MD simulation trajectories confirm the formation of stable complexes of Sunitinib with all six CDs. However, according to the distance analysis, it can be inferred that among all the natural and modified CDs, gamma-cyclodextrin and methylated-beta-cyclodextrin have the most dependable interaction complexes with Sunitinib. The reduced hydrogen bond formation with the solvent in inclusion complexes compared to free CDs indicates that Sunitinib displaces water molecules from the internal wall, highlighting the formation of hydrogen bonds between the CDs and Sunitinib and underscoring the potential of CDs for drug encapsulation. Interaction energy analysis emphasizes the significant role of van der Waals interactions in the encapsulation of Sunitinib within CDs and suggests that methylated-beta-cyclodextrin and beta-cyclodextrin are the optimal choices for the delivery of Sunitinib.

Graphical Abstract