Quantitative Purity–Activity
Relationships
of Natural Products: The Case of Anti-Tuberculosis Active Triterpenes
from <i>Oplopanax horridus</i>
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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 <i>Oplopanax
horridus</i> 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 <i>O. horridus</i> 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