https://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00163
https://www.ncbi.nlm.nih.gov/pubmed/31312409?dopt=Abstract
TITLE:
Antioxidant, Anti-inflammatory, and Neuroprotective Effects of Novel Vinyl Sulfonate Compounds as Nrf2 Activator.
DESCRIPTION:
Antioxidant, Anti-inflammatory, and Neuroprotective Effects of Novel Vinyl Sulfonate Compounds as Nrf2 Activator.
ACS Med Chem Lett. 2019 Jul 11;10(7):1061-1067
Authors: Choi JW, Shin SJ, Kim HJ, Park JH, Kim HJ, Lee EH, Pae AN, Bahn YS, Park KD
Abstract
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.
PMID: 31312409 [PubMed]
PMID:
PubMed:31312409
DATE FOUND:
07/18/19 06:03AM
LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31312409?dopt=Abstract