Vindeburnol: A natural product-inspired chemical tool for central nervous system drug design

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; (±)-(3α,14β)-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. Although few clinical trials were conducted, further development of vindeburnol was abandoned. This review presents synthetic approaches to vindeburnol synthesis as well as the most complete discussion of its pharmacological effects. Studies involving vindeburnol in animal models of CNS disorders and a few human trials have been presented in separate sections. Special attention is placed on derivatives and analogs based on the vindeburnol scaffold. The interesting pharmacological profile of vindeburnol suggests that this NP-inspired compound may serve as a useful tool or structural basis for next-generation molecules in CNS drug design and discovery.