Cytotoxic Monoterpenoid Indole Alkaloids from Tabernaemontana corymbosa as Potent Autophagy Inhibitors by the Attenuation of Lysosomal Acidification

J Nat Prod. 2020 May 22;83(5):1432-1439. doi: 10.1021/acs.jnatprod.9b00856. Epub 2020 May 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acids
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Autophagy / drug effects*
  • Circular Dichroism
  • Drug Screening Assays, Antitumor
  • HeLa Cells
  • Humans
  • Lysosomes / drug effects*
  • Lysosomes / metabolism*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Molecular Structure
  • Secologanin Tryptamine Alkaloids / chemistry*
  • Secologanin Tryptamine Alkaloids / pharmacology*
  • Tabernaemontana / chemistry*

Substances

  • Acids
  • Antineoplastic Agents, Phytogenic
  • Secologanin Tryptamine Alkaloids