Gracilin A Derivatives Target Early Events in Alzheimer's Disease: in Vitro Effects on Neuroinflammation and Oxidative Stress.

ABSTRACT: The search for compounds capable of targeting early pathological changes of Alzheimer̀s disease (AD), such as oxidative stress and neuroinflammation, is an important challenge. Gracilin A derivatives were recently synthesized, using a pharmacophore-directed retrosynthesis (PDR) strategy, and found to possess potent neuroprotective effects. In this work, the previously described derivatives 1-7 which demonstrated mitochondrial-mediated, antioxidant effects were chosen for further study. The ability of compounds to modulate the expression of antioxidant genes (CAT, GPx, SODs, and Nrf2) was determined in SH-SY5Y cells, and the simplified derivatives 2 and 3 were found to be the most effective. The anti-neuroinflammatory properties of all

SUBMITTER: Alvarino R 

PROVIDER: S-EPMC7654966 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature