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
Uncarialines A-E (1-5), five undescribed monoterpene indole alkaloids, together with five known analogues were obtained from the stems of Uncaria rhynchophylla. Alkaloids 1-3 were unique 3,4-seco-tricyclic alkaloids with a 6/5/10 ring system, while 4 and 5 possessed a rare rearranged scaffold originated from corynantheine-type alkaloids with C-2/C-7 oxidation. Their structures were characterized by a comprehensive analysis of MS, NMR, and ECD. Their effects on blood clotting times of human plasma were evaluated and alkaloid 5 had a slight prolongation effect on both thrombin time and activated partial thromboplastin time (p < 0.001).