Identification of molecular target of Vindeburnol and its derivatives

Natural products (NPs) often act as sources of CNS-active agents and provide inspiration for the development of synthetic molecules that incorporate their best features. Vindeburnol (VIND; (±)-(3a,14ß)-20,21-dinoreburnamenin-14-ol; developmental codes RU24722 or BC19), based on the core structure of eburnamine-vincamine alkaloids, has been extensively investigated for its biological activities. This molecule has demonstrated potential therapeutic properties in various in vivo models of CNS disorders such as multiple sclerosis, Alzheimer's disease, and depressive-like behavior. Many biochemical experiments which characterize vindeburnol influence on neuromediaters have been studied and published but molecular target in CNS is still unknown. Our research is new attempt to discover it. Overall design: Randomized controlled study comparing vindeburnol (n=5) and VB-127 derivative (n=6) versus untreated controls (n=6) in male C57BL/6 mice. Both compounds administered at 20 mg/kg/day oral gavage for 5 days. Locus coeruleus tissue collected 24h post-treatment for RNA-seq analysis.