Iqbal Kashif, Iqbal Javeid, Staerk Dan, Kongstad Kenneth T
Department of Pharmacology, Faculty of Pharmacy and Health Sciences, University of BalochistanQuetta, Pakistan.
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of CopenhagenCopenhagen, Denmark.
Front Pharmacol. 2017 May 31;8:337. doi: 10.3389/fphar.2017.00337. eCollection 2017.
This work describes an analytical platform based on semi-high-resolution antileishmanial profiling combined with hyphenation of high-performance liquid chromatography - high-resolution mass spectrometry - solid-phase extraction - nuclear magnetic resonance spectroscopy, i.e., HR-antileishmanial assay/HPLC-HRMS-SPE-NMR. The platform enables fast pinpointing of HPLC peaks representing inhibitors in complex matrices, with subsequent structural identification of targeted inhibitors. Active analytes were cumulatively trapped on SPE cartridges and the structures elucidated by analysis of NMR spectra obtained in the HPLC-HRMS-SPE-NMR mode. This led to the identification of six known compounds 2,4,6-trihydroxyacetophenone-2--β-D-glucopyranoside (), lalioside (), luteolin-4'--β-D-glucopyranoside (), apigenin-4'--β-D-glucopyranoside (), luteolin (), and apigenin (). IC of the active compounds were determined with luteolin being the most potent inhibitor with an IC value of 4.15 μg/ml. The platform proved to be an efficient method for the identification of inhibitors.
这项工作描述了一个分析平台，该平台基于半高分辨率抗利什曼原虫分析，并结合了高效液相色谱-高分辨率质谱-固相萃取-核磁共振光谱联用技术，即HR-抗利什曼原虫分析/HPLC-HRMS-SPE-NMR。该平台能够快速找出复杂基质中代表抑制剂的HPLC峰，并随后对目标抑制剂进行结构鉴定。活性分析物被累积捕获在SPE柱上，并通过分析HPLC-HRMS-SPE-NMR模式下获得的NMR光谱来阐明其结构。这导致鉴定出六种已知化合物：2,4,6-三羟基苯乙酮-2--β-D-吡喃葡萄糖苷（）、拉利苷（）、木犀草素-4'--β-D-吡喃葡萄糖苷（）、芹菜素-4'--β-D-吡喃葡萄糖苷（）、木犀草素（）和芹菜素（）。测定了活性化合物的半数抑制浓度（IC），其中木犀草素是最有效的抑制剂，IC值为4.15μg/ml。该平台被证明是一种鉴定抑制剂的有效方法。
