Computational studies on the structural variations of MAO-A and MAO-B inhibitors - An in silico docking approach-Supplementary data

ABSTRACT

The neurological disorder is a concerning problem in the present social scenario. The malfunction of the monoamine oxidase (MAO) enzyme is the responsible factor behind this disorder because this enzyme regulates the metabolism of monoamine neurotransmitters. This work aimed to design and propose the best MAO inhibitors through extensive computational analysis so that the favourable drug-like molecules could be identified for future synthesis. The drugs selected in this study were three MAO-A inhibitors namely Moclobemide, Tolxatone and Brofaromine and two MAO-B inhibitors namely Selegiline and Rasagiline. By substituting hydrophilic and hydrophobic groups at the specified positions, structural variations were designed for each drug. The designed variations and their parent drugs were optimized (basis set is B3LYP/6-311G(d, p)) and the optimized structures were docked to the target using PyRx software. The binding energy of each variation was compared to that of parent drug. The drug-likeness, physicochemical properties (solubility, polarity, flexibility, gastrointestinal absorption, saturation etc.) and toxicity of the lower binding energy variations were analysed using the swissADME, Osiris property explorer and ProTox-II servers. The interacting residues of the enzymes were obtained from the LigPlot+ program. The safe and low binding energy variations with favourable drug properties are suggested for further drug research