Estudio de derivados hemisintéticos por reducción de dehidroleucodina

Abstract

Abstract:Dehydroleucodine is a guaianolide-type sesquiterpene lactone abundant in the aerial parts of the shrub Gynoxys verrucosa Wedd., which has proven to be a molecule with a wide range of applications regarding its biological activity. Due to its antibacterial properties against Methicillin Resistant Staphylococcus aureus (MRSA), its cytostatic effects by inducing cell cycle arrest, apoptosis, DNA damage in astrocytoma D-834 through p73/p53 regulation and its cytotoxic activity against some Acute Myeloid Leukemia cell lines by inhibiting NF-kB, structurally attributed to the presence trans α-Metylene-γ-lactone ring, that it might be considered as a promissory chemotherapeutic agent. In order to study the reduction of dehydroleucodine carbonyl group at the α,β unsaturated cyclopentenone system for the development of new molecules with cytotoxic activity against Acute Myeloid Leukemia, we performed some hemisynthetic reactions involving the use of NaBH4 in cold methanolic media and Luche reduction conditions. Even though, we were not able to obtain the hemisynthetic target derivative, interestingly we observed the efficient and selective reduction of the trans α-Metylene-γ-lactone system to the correspondent 6,12-Dihydroxy-guain-3,10,11-trien-2-one.