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

•Synthesis of (E)−2-(2-aminothiazol-4-yl)-N'-(substituted benzylidene)acetohydrazide (3a-e).•Synthesis of heterocyclic selenium nanoparticles (3a-e)-SeNPs in situ using benzylidene-acetylhydrazide 3a-e.•In vitro hMAOA and hMAOB inhibition assay.•Molecular docking against hMAO-B (pdb code: 2V5Z) and hMAO-A (pdb code:2Z5X).•Anti-Parkinson ability of 3b and 3b(SeNPs) was investigated in the current study in the haloperidol-induced parkinson's rat model. Structure –anti-tubercular activity. 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. [Display omitted]