Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago , Chicago, Illinois 60612, USA.
J Nat Prod. 2013 Mar 22;76(3):413-9. doi: 10.1021/np3007809. Epub 2013 Jan 28.
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.
本研究对先前开发的纯度-活性关系（PAR）概念进行了扩展，使人们能够定量评估多种微量成分对剩余复杂天然产物生物活性的影响。从阿拉斯加民族植物学的刺五加（Oplopanax horridus）中选择具有抗结核活性的三萜类化合物作为开发定量 PAR（QPAR）概念的案例。通过 1D-和 2D-NMR 对纯化三萜类化合物的残余复杂性进行了初步评估，并确定为结构相关和不相关杂质的组合。使用生化计量学方法，通过线性回归分析将 O. horridus 三萜类化合物的连续色谱馏分的 qHNMR 纯度和抗结核活性相关联，生成数学 QPAR 模型。结果表明，杂质（如广泛存在的单甘油酯）可能对富含三萜类化合物的馏分的观察到的抗分枝杆菌活性产生深远影响。QPAR 概念能够在剩余复杂组成对天然产物生物活性有贡献的情况下提供定量评估。
