| Literature DB >> 31312409 |
Ji Won Choi1, Su Jeong Shin1,2, Hyeon Ji Kim1,2, Jong-Hyun Park1, Hyeon Jeong Kim1,2, Elijah Hwejin Lee1, Ae Nim Pae1,3,4, Yong Sun Bahn2, Ki Duk Park1,3,4.
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.Entities:
Year: 2019 PMID： 31312409 PMCID： PMC6627712 DOI： 10.1021/acsmedchemlett.9b00163
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345