ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Inclusion complexes of natural and modified cyclodextrins with nilotinib anticancer drug: insights from molecular docking and molecular dynamics simulation

Leila Hokmabady and Elham Mohebbi

Department of Chemistry, Faculty of Science, Payame Noor University (PNU), Tehran, Iran

E-mail: l.hokmabadi@pnu.ac.ir

Received: 6 March 2025  Accepted: 26 August 2025

Abstract:

This study investigates the potential of natural and modified cyclodextrins in forming stable inclusion complexes with nilotinib, a chemotropic drug and tyrosine kinase inhibitor. Computational techniques, including molecular docking and molecular dynamics simulation, evaluate the capability of various natural cyclodextrins (alpha-cyclodextrin, beta-cyclodextrin, and gamma-cyclodextrin) and modified cyclodextrins (random methyl beta-cyclodextrin, amino beta-cyclodextrin, and hydroxypropyl beta-cyclodextrin) to form inclusion complexes with nilotinib. Results from both molecular docking and molecular dynamics simulations confirm stable inclusion complexes formation between nilotinib and all cyclodextrins. However, when nilotinib is included and water molecules are released, there is a reduction in hydrogen bonds formed between solvent molecules and the encapsulated cyclodextrins compared to free cyclodextrins. hydroxypropyl beta-cyclodextrin exhibits the highest number of hydrogen bonds with nilotinib, while alpha-cyclodextrin exhibits the least. The hydroxypropyl groups in hydroxypropyl beta-cyclodextrin can form hydrogen bonds with solvent molecules and the drug, resulting in a higher average number of hydrogen bonds than other cyclodextrins in the inclusion complexe-solvent system. These findings suggest the potential use of hydroxypropyl beta-cyclodextrin formulation to improve bioavailability and enable targeted drug delivery for the treatment of chronic myeloid leukemia, acute lymphoblastic leukemia, and gastrointestinal stromal tumors.

Keywords: Nilotinib; Natural cyclodextrins; Modified cyclodextrins; Molecular docking; Molecular dynamics (MD) simulation

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-025-04352-6

Chemical Papers 79 (12) 8799–8814 (2025)