Choi, Ji Won Shin, Su Jeong Kim, Hyeon Ji Park, Jong-Hyun Kim, Hyeon Jeong Lee, Elijah Hwejin Pae, Ae Nim Bahn, Yong Sun Park, Ki Duk 2024-01-19T19:34:15Z 2024-01-19T19:34:15Z 2021-09-02 2019-07 1948-5875 https://pubs.kist.re.kr/handle/201004/119829 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.S-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. English AMER CHEMICAL SOC TRANSCRIPTION FACTOR NRF2 PARKINSONS-DISEASE DOPAMINERGIC-NEURONS OXIDATIVE STRESS MOUSE MODEL DEFICIENCY MECHANISMS PARAMETERS DECLINE PATHWAY Antioxidant, Anti-inflammatory, and Neuroprotective Effects of Novel Vinyl Sulfonate Compounds as Nrf2 Activator Article 10.1021/acsmedchemlett.9b00163 1 ACS MEDICINAL CHEMISTRY LETTERS, v.10, no.7, pp.1061 - 1067 ACS MEDICINAL CHEMISTRY LETTERS 10 7 1061 1067 scie scopus 000475543200010 2-s2.0-85067409345 Chemistry, Medicinal Pharmacology & Pharmacy Article TRANSCRIPTION FACTOR NRF2 PARKINSONS-DISEASE DOPAMINERGIC-NEURONS OXIDATIVE STRESS MOUSE MODEL DEFICIENCY MECHANISMS PARAMETERS DECLINE PATHWAY Parkinson&apos s disease antioxidant anti-inflammatory Nrf2/Keapl pathway MPTP mouse model vinyl sulfone