Biological Activity and Stability Analyses of Knipholone Anthrone, a Phenyl Anthraquinone Derivative Isolated From Kniphofia Foliosa Hochst

J Pharm Biomed Anal. 2019 Sep 10;174:277-285. doi: 10.1016/j.jpba.2019.05.065. Epub 2019 May 31.

Abstract

Knipholone (1) and knipholone anthrone (2), isolated from the Ethiopian medicinal plant Kniphofia foliosa Hochst. are two phenyl anthraquinone derivatives, a compound class known for biological activity. In the present study, we describe the activity of both 1 and 2 in several biological assays including cytotoxicity against four human cell lines (Jurkat, HEK293, SH-SY5Y and HT-29), antiplasmodial activity against Plasmodium falciparum 3D7 strain, anthelmintic activity against the model organism Caenorhabditis elegans, antibacterial activity against Aliivibrio fischeri and Mycobacterium tuberculosis and anti-HIV-1 activity in peripheral blood mononuclear cells (PBMCs) infected with HIV-1c. In parallel, we investigated the stability of knipholone (2) in solution and in culture media. Compound 1 displays strong cytotoxicity against Jurkat, HEK293 and SH-SY5Y cells with growth inhibition ranging from approximately 62-95% when added to cells at 50 μM, whereas KA (2) exhibits weak to strong activity with 26, 48 and 70% inhibition of cell growth, respectively. Both 1 and 2 possess significant antiplasmodial activity against Plasmodium falciparum 3D7 strain with IC50 values of 1.9 and 0.7 μM, respectively. These results complement previously reported data on the cytotoxicity and antiplasmodial activity of 1 and 2. Furthermore, compound 2 showed HIV-1c replication inhibition (growth inhibition higher than 60% at tested concentrations 0.5, 5, 15 and 50 μg/ml and an EC50 value of 4.3 μM) associated with cytotoxicity against uninfected PBMCs. The stability study based on preincubation, HPLC and APCI-MS (atmospheric-pressure chemical ionization mass spectrometry) analysis indicates that compound 2 is unstable in culture media and readily oxidizes to form compound 1. Therefore, the biological activity attributed to 2 might be influenced by its degradation products in media including 1 and other possible dimers. Hence, bioactivity results previously reported from this compound should be taken with caution and checked if they differ from those of its degradation products. To the best of our knowledge, this is the first report on the anti-HIV activity and stability analysis of compound 2.

Keywords: Knipholone anthrone; Medicinal plants; Natural products; Stability analysis; anti-HIV activity.

MeSH terms

  • Animals
  • Anthelmintics / pharmacology
  • Anthracenes / analysis*
  • Anthracenes / pharmacology*
  • Anthraquinones / pharmacology*
  • Anti-Bacterial Agents / pharmacology
  • Anti-HIV Agents / pharmacology*
  • Antimalarials / pharmacology
  • Biological Assay
  • Caenorhabditis elegans / drug effects
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Drug Evaluation, Preclinical
  • HEK293 Cells
  • Humans
  • Jurkat Cells
  • Leukocytes, Mononuclear / drug effects*
  • Liliaceae / chemistry
  • Molecular Structure
  • Mycobacterium tuberculosis
  • Plant Extracts / pharmacology
  • Plants, Medicinal / chemistry
  • Plasmodium falciparum / drug effects

Substances

  • Anthelmintics
  • Anthracenes
  • Anthraquinones
  • Anti-Bacterial Agents
  • Anti-HIV Agents
  • Antimalarials
  • Plant Extracts
  • knipholone anthrone