Estudo computacional da interação de fármacos anti-Parkinson com nanoestruturas de carbono

Abstract

One of the consequences of increased life expectancy is the higher incidence of cases of neurodegenerative diseases, more common in older people. The most present in this category are: Alzheimer's disease and Parkinson's disease. The treatment of patients with Parkinsonism is often extremely exhausting, full of adverse effects; in certlin cares, the use of anti-Parkinson's drugs must cease so that individuals do not die or have permanent sequelae. Non-toxic nanostructured carbon particles interact with drugs, forming supramolecules capable of crossing the blood-brain barrier more easily, this show characteristics of good drug delivers. The present work aims to computationally study the interaction of the anti-Parkinson drugs Levodopa (LDP), Carbidopa (CDP), Entacapone (ECP) and Benserazide (BZD) with carbon nanostructures: Fullerane (C60), Single-walled carbon nanotube (NTCPS) and Fullerol (C60OH24) with the purpose of evaluating the application of these nanoparticles in a Drug delivery system. Molecular properties were obtained using DFT-level calculations, aiming to correlate them with pharmacological activity, as well as estimating the preferential adsorpition sites. The drug-nanostructure interactions were made using Monte Carlo and Molecular Dynamics Methods, obtaining the interaction energies and preferred orientations. It was observed that the interaction of drugs with C60 and NTCPS resulted in physical adsorption, where ECP binds more strongly to nanostructures, followed by LDP, BZD and CDP respectively, results attributed to molecular properties, such as LUMO and the electron density distribution in drugs. In the interaction of the molecules with C60OH24, chemisorption was observed, a consequence of the interaction of the heteroatoms of the drugs with the hydroxyl groups of the nanostructure, the interaction force undergoes a change and is shown as: ECP > BZD > CDP > LDP. As a final consideration, we have a potential suggestion for the treatment of Parkinson's disease would be the administration of LDP and CDP together with the carbon nanotube, making the drugs adhere to the carbon structure, facilitating the passage of drugs through the blood-brain barrier and potentially be released in the brain region, thus ensuring better use of the pharmacological effects of the drugs.