Antiproliferative Alkaloids from Alangium longiflorum, an Endangered Tropical Plant Species

J Nat Prod. 2018 Aug 24;81(8):1884-1891. doi: 10.1021/acs.jnatprod.8b00411. Epub 2018 Aug 14.

Abstract

Alangium longiflorum is currently in extinction crisis, which will likely severely hamper further phytochemical investigation of this plant species from new collections. A crude extract of leaves of A. longiflorum (N33539), collected for the U.S. National Cancer Institute in 1989, showed potent cancer cell line antiproliferative activity. A phytochemical study resulted in the isolation of 17 secondary metabolites, including two new tetrahydroisoquinoline alkaloids, 8-hydroxytubulosine (1) and 2'- O- trans-sinapoylisoalangiside (2), as well as a new sinapolyloxylupene derivative (3). Using in-house assays and NCI-60 panel screening, compound 1 displayed broad-spectrum inhibitory activity at submicromolar levels against most tested tumor cell lines, except for drug-transporter-overexpressing cells. Compound 1 caused accumulation of sub-G1 cells with no effect on cell cycle progression, suggesting that this substance is an apoptosis inducer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alangiaceae / chemistry*
  • Alkaloids / chemistry*
  • Alkaloids / pharmacology*
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Endangered Species
  • G1 Phase / drug effects
  • Humans
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology

Substances

  • Alkaloids
  • Antineoplastic Agents, Phytogenic
  • Plant Extracts