Brassinosteroids and analogs as neuroprotectors: Synthesis and structure–activity relationships

We have demonstrated previously that the brassinosteroid (BR) 24-epibrassinolide exerts neuroprotective effects deriving from its antioxidative properties. In this study, we synthesized 2 natural BRs and 5 synthetic analogs and analyzed their neuroprotective actions in neuronal PC12 cells, against 1-methyl-4-phenylpyridinium (MPP+), a neurotoxin known to induce oxidative stress and degenerescence of dopaminergic neurons characteristic of Parkinsonian brains. We also tested the neuroprotective potential of 2 commercially available BRs. Our results disclosed that 6 of the 9 BRs and analogs tested protected neuronal PC12 cells against MPP+ toxicity. In addition, our structure–activity study suggests that the steroid B-ring and lateral chain play an important role for their neuroprotective action.

► We synthesized 2 natural BRs and 5 synthetic analogs. ► Neuroprotective action in neuronal PC12 cells, against MPP+ was tested. ► Some brassinosteroids exhibit neuroprotection. ► Steroid B-ring and lateral chain functionalities are important for neuroprotection.