Quantitative purity-activity relationships of natural products: the case of anti-tuberculosis active triterpenes from Oplopanax horridus.
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.
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago , Chicago, Illinois 60612, USA.
Feng
F
Qiu
Geping
G
Cai
Birgit U
BU
Jaki
David C
DC
Lankin
Scott G
SG
Franzblau
Guido F
GF
Pauli
D000413:Alaska; D000995:Antitubercular Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D019906:Nuclear Magnetic Resonance, Biomolecular; D028002:Oplopanax / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D000995:Antitubercular Agents; D001688:Biological Products; D014315:Triterpenes