Abstract
Ramalin, a strong antioxidant isolated from Antarctic lichens, has been shown to have potential therapeutic effects in the treatment of Alzheimer's disease. However, this compound is readily degraded in aqueous solutions, which restricts its development as a therapeutic agent. With a view toward addressing this problem, in this study, we modified the structure of ramalin to obtain more stable compounds and attempted to identify a derivative with the strongest neuroprotective properties. We synthesized a total of 20 ramalin derivatives, among which, RA-2N was demonstrated to have the best neuroprotective effects, not only inhibiting inflammation in BV2 cells but also inhibiting inflammation-induced HT22 cell apoptosis in BV2-HT22 co-culture models. Moreover, we established that these effects were associated with an inhibition of the nuclear translocation of nuclear factor kappa-B (NF-κB). Our findings in this study revealed that the synthesis of ramalin derivatives is an effective approach for stabilizing this compound for therapeutic purposes. Given its modified structure, the RA-2N derivative can inhibit inflammation and protect nerve cells, and thus indicate its potential application as a drug for treating neurodegenerative diseases.
Published Version
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