Cytotoxic Monoterpenoid Indole Alkaloids from <i>Tabernaemontana corymbosa</i> as Potent Autophagy Inhibitors by the Attenuation of Lysosomal Acidification
Yu Zhang, Xiao Ding, Yu-Xi Yuan, Ling‐Li Guo, Xiao‐Jiang Hao
Abstract
Twenty-six alkaloids, including the new taberines A–I (1–9), were obtained from Tabernaemontana corymbosa. The structures and absolute configurations were elucidated via MS, NMR, and ECD spectroscopic data analyses. Alkaloids 1–4 are new vobasinyl-ibogan alkaloids, and 1 is characterized by an unusual 1,3-oxazinane moiety. Alkaloids 4 and 16 exhibited moderate cytotoxic potency against various human cancer cell lines, while 4, 10, 11, 13, 14, and 16 showed attenuation of lysosomal acidification activity (EC50: 12.9–29.8 μM), thereby inhibiting autophagic flux.
Topics & Concepts
ApocynaceaeAlkaloidAutophagyStereochemistryIndole alkaloidMoietyChemistryPharmacognosyIndole testBiologyBiological activityBiochemistryIn vitroBotanyApoptosisAlkaloids: synthesis and pharmacologyGinseng Biological Effects and ApplicationsNatural product bioactivities and synthesis