Oxazolopyridines and thiazolopyridines as monoamine oxidase B inhibitors for the treatment of Parkinson's disease
| Autor: | Bongjin Moon, Taekeun Kim, Jiyoon Kim, Jaeick Lee, Eun Jeong Lim, Ki Duk Park, Hyunah Choo, Gyochang Keum, Miyoung Yeom, Sun-Joon Min, Seonmi Jo, Il Han Choo, C. Justin Lee, Hyeri Park, Ghilsoo Nam |
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| Rok vydání: | 2013 |
| Předmět: |
Parkinson's disease
Monoamine Oxidase Inhibitors Pyridines Dopamine Clinical Biochemistry Pharmaceutical Science Pharmacology Biochemistry chemistry.chemical_compound Structure-Activity Relationship Biosynthesis Catalytic Domain Drug Discovery medicine Humans Molecular Biology IC50 Monoamine Oxidase Oxazoles chemistry.chemical_classification Binding Sites Catabolism Organic Chemistry Dopaminergic Parkinson Disease medicine.disease Recombinant Proteins Molecular Docking Simulation Thiazoles Enzyme chemistry Molecular Medicine Monoamine oxidase B medicine.drug |
| Zdroj: | Bioorganicmedicinal chemistry. 21(17) |
| ISSN: | 1464-3391 |
| Popis: | In Parkinson's disease, the motor impairments are mainly caused by the death of dopaminergic neurons. Among the enzymes which are involved in the biosynthesis and catabolism of dopamine, monoamine oxidase B (MAO-B) has been a therapeutic target of Parkinson's disease. However, due to the undesirable adverse effects, development of alternative MAO-B inhibitors with greater optimal therapeutic potential towards Parkinson's disease is urgently required. In this study, we designed and synthesized the oxazolopyridine and thiazolopyridine derivatives, and biologically evaluated their inhibitory activities against MAO-B. Structure-activity relationship study revealed that the piperidino group was the best choice for the R(1) amino substituent to the oxazolopyridine core structure and the activities of the oxazolopyridines with various phenyl rings were between 267.1 and 889.5nM in IC50 values. Interestingly, by replacement of the core structure from oxazolopyrine to thiazolopyridine, the activities were significantly improved and the compound 1n with the thiazolopyridine core structure showed the most potent activity with the IC50 value of 26.5nM. Molecular docking study showed that van der Waals interaction in the human MAO-B active site could explain the enhanced inhibitory activities of thiazolopyridine derivatives. |
| Databáze: | OpenAIRE |
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