RESUMO
Eleven monoterpenoid indole alkaloids, including three new ones, tabercrassines A-C (1-3), were isolated from the seeds of Tabernaemontana crassa. Tabercrassine A (1) is an ibogan-ibogan-type bisindole alkaloid which is formed by the polymerization of two classic ibogan-type monomers through a C3 unit aliphatic chain. Their structures were established by extensive analysis of HRESIMS, NMR, and ECD spectra. Cellular assays showed that alkaloids 1-3 all reduce Aß42 production and inhibit phospho-tau (Thr217), a new biomarker of Alzheimer's disease [AD] associated with BACE1-, NCSTN-, GSK3ß-, and CDK5-mediated pathways, suggesting these alkaloids' potential against AD.
Assuntos
Antineoplásicos Fitogênicos , Alcaloides de Triptamina e Secologanina , Tabernaemontana , Alcaloides de Triptamina e Secologanina/farmacologia , Alcaloides de Triptamina e Secologanina/química , Alcaloides Indólicos/farmacologia , Tabernaemontana/química , Secretases da Proteína Precursora do Amiloide , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Ácido Aspártico Endopeptidases , Estrutura MolecularRESUMO
Two new alkaloids, taberdines L (1) and M (2), together with six known alkaloids, were isolated from the twigs and leaves of Tabernaemontana divaricata. Taberdine L (1) represents the first optically active natural member of the allo iboga class of alkaloids with the ethyl side chain in a bridgehead position. Their structures including absolute configuration were elucidated by a combination of MS, NMR, and ECD calculation. The in vitro cytotoxic activities of 1 and 2 against five human cancer cell lines were also evaluated.