Antioxidant, Anti-inflammatory, and Neuroprotective Effects of Novel Vinyl Sulfonate Compounds as Nrf2 Activator
Autor: | Ki Duk Park, Ae Nim Pae, Jong Hyun Park, Su Jeong Shin, Hyeon Jeong Kim, Jiwon Choi, Hyeon Ji Kim, Yong Sun Bahn, Elijah Hwejin Lee |
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Rok vydání: | 2019 |
Předmět: |
Antioxidant
medicine.drug_class medicine.medical_treatment macromolecular substances Vinyl sulfone medicine.disease_cause environment and public health 01 natural sciences Biochemistry Neuroprotection Medicinal chemistry Anti-inflammatory Nrf2 activation chemistry.chemical_compound Drug Discovery medicine chemistry.chemical_classification 010405 organic chemistry Chemistry organic chemicals Organic Chemistry technology industry and agriculture respiratory system 0104 chemical sciences 010404 medicinal & biomolecular chemistry Enzyme Sulfonate Oxidative stress |
Zdroj: | ACS Med Chem Lett |
ISSN: | 1948-5875 |
Popis: | [Image: see text] The main pathway responsible for cellular regulation against oxidative stress is nuclear factor E2-related factor-2 (Nrf2) signaling. We previously synthesized and reported a novel vinyl sulfone (1) as an Nrf2 activator with therapeutic potential for Parkinson’s disease (PD). In this study, we changed the vinyl sulfone to vinyl sulfonamide or vinyl sulfonate to improve Nrf2 activating efficacy. We observed that the introduction of vinyl sulfonamide led to a reduction of the effects on Nrf2 activation, whereas vinyl sulfonate compounds exhibited superior activity compared to the vinyl sulfone compounds. Among the vinyl sulfonates, 3c exhibited 6.9- and 83.5-fold higher effects on Nrf2 activation than the corresponding vinyl sulfone (1) and vinyl sulfonamide (2c), respectively. Compound 3c was confirmed to induce expression of the Nrf2-dependent antioxidant enzymes at the protein level in cells. In addition, 3c mitigated PD-associated behavioral deficits by protecting DAergic neurons in the MPTP-induced mouse model of PD. |
Databáze: | OpenAIRE |
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