Quantitative purity-activity relationships of natural products: the case of anti-tuberculosis active triterpenes from Oplopanax horridus

J Nat Prod. 2013 Mar 22;76(3):413-9. doi: 10.1021/np3007809. Epub 2013 Jan 28.

Abstract

The present study provides an extension of the previously developed concept of purity-activity relationships (PARs) and enables the quantitative evaluation of the effects of multiple minor components on the bioactivity of residually complex natural products. The anti-tuberculosis active triterpenes from the Alaskan ethnobotanical Oplopanax horridus were selected as a case for the development of the quantitative PAR (QPAR) concept. The residual complexity of the purified triterpenes was initially evaluated by 1D- and 2D-NMR and identified as a combination of structurally related and unrelated impurities. Using a biochemometric approach, the qHNMR purity and anti-TB activity of successive chromatographic fractions of O. horridus triterpenes were correlated by linear regression analysis to generate a mathematical QPAR model. The results demonstrate that impurities, such as widely occurring monoglycerides, can have a profound impact on the observed antimycobacterial activity of triterpene-enriched fractions. The QPAR concept is shown to be capable of providing a quantitative assessment in situations where residually complex constitution contributes toward the biological activity of natural products.

MeSH terms

  • Alaska
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / isolation & purification*
  • Antitubercular Agents / pharmacology*
  • Biological Products / chemistry
  • Biological Products / isolation & purification*
  • Biological Products / pharmacology*
  • Fruit / chemistry
  • Humans
  • Models, Biological
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects
  • Nuclear Magnetic Resonance, Biomolecular
  • Oplopanax / chemistry*
  • Quantitative Structure-Activity Relationship
  • Triterpenes / chemistry
  • Triterpenes / isolation & purification*
  • Triterpenes / pharmacology*

Substances

  • Antitubercular Agents
  • Biological Products
  • Triterpenes