SCAFFOLD BASED DESIGNING OF NOVEL 1, 3-DIOXOL DERIVATIVES AS MONOAMINE OXIDASE INHIBITOR: IN SILICO APPROACH

Abstract

Monoamine oxidase (MAO) catalyzes the oxidative deamination of monoamine neurotransmitters such as serotonin, dopamine, norepinephrine, and appears to play important role in many psychiatric and neurological disorders. MAO-A metabolizes serotonin and nor adrenaline and is inhibited by the low concentration of clorgyline. MAO-A inhibitors are useful in the therapy of mental disorders as antidepressants and anxiety. Therefore, this makes it a potential target for the development of novel therapies. In the present study, a series of seventy novel 1, 3-dioxol derivatives were designed as MAO- A inhibitors by using in silico approaches and nine best compounds were synthesized from the designed series. We assume the significance of computational methods in designing of novel derivatives for desired pharmacological activity. QSAR, pharmacophore, ADME methods, Auto dock techniques were used to design MAO-A inhibitors. A Ligand-based drug design was employed to optimize SP-149 and SP-150 as efficacious and potent MAO-A inhibitors. The best compound, SP-149, showed 10.42 ± 1.78 nmol/mg MAO-A inhibitory activity with -5.37 Kcal/mol binding energy.