Alkylated resveratrol prodrugs and metabolites as potential therapeutics for neurodegenerative diseases.

摘要: Abstract Resveratrol is a naturally occurring stilbene which has shown promising results as treatment for several neurodegenerative diseases. However, its application limited due to low efficacy and bioavailability. Here, we have designed synthesized alkylated resveratrol prodrugs combining structural modification improve antioxidant anti-inflammatory properties the preparation of extend drug For comparison also studied derivatives. Methylated butylated derivatives showed best in vitro neuroprotective activity. The glucosyl- glucosyl-acyl- these lower toxicity on zebra fish embryo. When neuroprotection was examined pentylenetetrazole challenged fish, they were capable reverting neuronal damage but extent than resveratrol. Nevertheless, 3-O-(6′-O-octanoyl)-β- d -glucopyranoside (compound 8) recovered AChE activity over 100% whereas only up 92%. In 3-nitropropionic acid mice model Huntington's disease, derivative 8 delayed onset reduced severity HD-like symptoms, by improving locomotor protecting against weight loss. Its effects involved an equal better profile SOD2 expression in brain tissue circulating levels IL-6 (11 vs 18 pg/mL), respectively. Finally, octanoyl chain compound could be playing role inflammation development indicating it acting double-drug, instead prodrug.