Synthesis, In-Vitro, In-Vivo screening, and molecular docking of disubstituted aminothiazole derivatives and their selenium nanoparticles as potential antiparkinson agents

Abstract

Neurological illnesses are among the leading causes of mortality across the world. In the present work, the synthesis of a new series of substituted aminothiazole derivatives (3a-e) as antiparkinsonian agents is reported. Furthermore, aminothiazoles 3a-e were used for in-situ synthesis of selenium nanoparticles 3a(SeNP)-3e(SeNP) to boost the CNS activities and potency. Selenium nanoparticles were confirmed using UV–Vis spectrophotometry, TEM, particle size distribution, and zeta potential. All selenium nano-sized forms elicited greater in-vitro inhibitory activity against both hMAO isoforms when compared to their corresponding normal-sized ones. Compound 3b was the most potent MAO-B inhibitor with an IC50 value of 0.11 µM. Its nano-sized form 3b(SeNP) showed improved hMAO-B inhibitory activity with an IC50 value of 0.033 µM which surpasses its normal-sized action (3b) by 70%. Molecular docking studies of compound 3b displayed interaction at the active sites of both hMAO-A and hMAO-B isoforms in an inhibitory mode similar to co-crystalized ligands. The antiparkinson effect of both 3b and 3b(SeNP) was further screened by using an in-vivo model of haloperidol-induced Parkinson's disease in rats. Behavioral tests in rats revealed that the nanoparticle formulation showed a superior effect on exploratory activity as an antiparkinsonian agent. Accordingly, this nanotechnology-based approach can be a promising lead for developing novel and potent treatments for neurodegenerative diseases.