Cytotoxic bufadienolides from the leaves of a medicinal plant Melianthus comosus collected in South Africa

Bioorg Chem. 2020 Sep:102:104102. doi: 10.1016/j.bioorg.2020.104102. Epub 2020 Jul 15.

Abstract

From the leaves of South African medicinal plant Melianthus comosus, four previously undescribed bufadienolides, 16β-formyloxymelianthugenin (1), 2β-acetoxymelianthusigenin (2), 2β-hydroxy-3β,5β-di-O-acetylhellebrigenin (3), and 2β-acetoxy-5β-O-acetylhellebrigenin (4) were isolated together with two known bufadienolides. The structural elucidation of the compounds was based on 1D and 2D NMR spectroscopy, high-resolution mass spectrometry, and other spectroscopic methods. The relative configurations were determined by single-crystal X-ray crystallography analysis and NOESY correlations. The isolated compounds displayed strong cytotoxicity against MCF-7 breast cancer cells, sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells. Compound 1 showed the most potent activity, with IC50 values of 0.07 μM towards CCRF-CEM, 0.06 μM towards CEM/ADR5000 and 0.36 μM towards MCF-7 followed by compound 4 with IC50 values of 0.13 μM towards CCRF-CEM, 0.08 μM towards CEM/ADR5000 and 0.53 μM towards MCF-7.

Keywords: Bufadienolides; Cytotoxicity; Melianthaceae; Melianthus comosus; Occurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Bufanolides / chemistry
  • Bufanolides / isolation & purification
  • Bufanolides / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Conformation
  • Plant Leaves / chemistry*
  • Plants, Medicinal / chemistry*
  • South Africa
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Phytogenic
  • Bufanolides