Synthesis and Biological Evaluation of Novel Ramalin Derivatives as Multi-Target Agents for Alzheimer’s Disease

Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by cognitive decline, oxidative stress, neuroinflammation, amyloid-beta (Aβ) accumulation, and tau protein hyperphosphorylation. In this study, we synthesized novel Ramalin derivatives and evaluated their therapeutic pote...

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Main Authors: Tai Kyoung Kim, Ju-Mi Hong, Yongeun Cho, Yeji Jeon, Heewon Cho, Jeongmi Lee, Jaewon Kim, Kyung Hee Kim, Il-Chan Kim, Se Jong Han, Hyuncheol Oh, Dong-Gyu Jo, Joung Han Yim
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/9/2030
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Summary:Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by cognitive decline, oxidative stress, neuroinflammation, amyloid-beta (Aβ) accumulation, and tau protein hyperphosphorylation. In this study, we synthesized novel Ramalin derivatives and evaluated their therapeutic potential against AD, focusing on antioxidant, anti-inflammatory, and neuroprotective activities. RA-2OMe, RA-4OMe, RA-2CF3, and RA-4OCF3 showed strong antioxidant effects, while RA-2OMe exhibited potent NO and NLRP3 inhibition (~20%). RA-NAP, RA-PYD, and RA-2Q showed moderate anti-inflammatory activity. BACE-1 inhibition was significant in RA-3CF3, RA-NAP, and RA-PYD, with IC<sub>50</sub> values lower than that of positive control, indicating greater inhibitory potency. RA-NAP and RA-PYD effectively inhibited both Aβ and tau aggregation, highlighting their multi-target potential for AD therapy. These findings indicate that Ramalin derivatives exhibit potential for multi-target activity in AD treatment. However, further studies on their pharmacokinetics, in vivo efficacy, and long-term safety are required to confirm their therapeutic applicability.
ISSN:1420-3049