Background:
Drugs used for Parkinson's disease (PD) are mainly responsible for only
relieving major symptoms, but may present several side effects that are typical of such pharmacological
treatment.
Methods:
This study aimed to use in silico methods for drug designing inhibitors of the PD therapeutic
target, monoamine oxidase B (MAO-B). Thus, 20 MAO-B inhibitors from the BindingDB
database were selected followed by a calculation of their descriptors at DFT B3LYP/6-31G**
level of theory.
Results:
Statistical analysis considering a Pearson correlation matrix led to the selection of electrophilicity
index as a descriptor related to the biological activity of inhibitors. Furthermore, based
on the prediction of suitable ADME/Tox properties, the molecule CID 54583085 was selected as a
template to carry out structural modifications to obtain 3 analogues, whereas molecules B and C
showed significant improvement in mutagenicity and carcinogenicity, in relation to the template.
Conclusion:
Thus, it is concluded that the proposed modifications led us to satisfactory results,
since there was an improvement in the toxicological properties of molecules, however, further
studies must be carried out to evaluate their biological activities as possible MAO-B inhibitors for
PD treatment.
Monoamine oxidase-B (MAO-B) inhibitors: implications for disease-modification in Parkinson’s disease
