Molecular docking and DFT study of rasagiline derivatives with MAO enzymes and their interaction with carbon nanostructure-based nanocarriers

Abstract

Developing effective neuroprotective therapies requires not only the design of potent enzyme inhibitors but also efficient delivery systems capable of crossing biological barriers. To address this, the present study employs a dual computational framework, integrating Density Functional Theory (DFT) calculations and molecular docking simulations, to evaluate rasagiline derivatives as potential monoamine oxidase (MAO) A and B inhibitors and to assess their delivery via carbon-based nanocarriers, C₆₀ fullerene, carbon nanosheets (CNS), and carbon nanotubes (CNT). DFT analysis revealed that C₆₀ fullerene is the most suitable nanocarrier, exhibiting optimal adsorption strengths ranging from −0.23 (gas phase) to −0.40 eV (aqueous phase). The formation of stable rasagiline-fullerene complexes, governed by non-covalent interactions, induced significant electronic modulation in the derivatives, thereby suggesting enhanced chemical reactivity and favorable delivery compatibility. Molecular docking studies further demonstrated isoform-specific inhibition, with derivative R6 exhibiting the highest affinity for MAO-A (binding energy −5.15 kcal/mol) and derivative R4 showing the strongest interaction with MAO-B (−8.58 kcal/mol). Collectively, the findings demonstrate that rasagiline derivatives possess strong inhibitory potential against MAO isoforms. Furthermore, the excellent stability of C₆₀ fullerene and its ability to serve as a nanocarrier for R4 through weak physical interactions make it a promising nanoplatform for targeted and efficient delivery.