title: An integrated strategy of ultra-high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry and virtual screening for the identification of α-glucosidase inhibitors in acarviostatin-containing complex.
abstract: We propose a strategy that integrates ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) and virtual docking to identify inhibitors of multiple human -glucosidases. UPLC yielded AIB656, an acarviostatin-containing complex, which was analyzed by Q-TOF-MS to acquire structural information and was tested for inhibition of N-terminal (MGAM-N), C-terminal (MGAM-C) catalytic domain of maltase-glucoamylase, and human pancreatic -amylase (HPA).A systematic computational study was performed to evaluate the inhibition activity for 51 identified acarviostatins with various sizes, including trace or difficult-to-prepare ingredients. We evaluated the selectivities of three -glucosidases to acarviostatins and revealed the strong inhibition of MGAM-Nby acarviostatin I0-1. The high accuracy of the dual-screening was validated using enzyme inhibition assays, and docking was suggested as a possible mechanism for the strong inhibition of MGAM-N by acarviostatin I0-1 and of MGAM-C by acarbose (acarviostatin I01). No compound in AIB656 was suitable for inhibiting all three -glucosidases. Compared with conventional chromatographic separation and inhibitory activity detection, integrating UPLC/Q-TOF-MS identification and virtual validation was more convenient and more reliable. This strategy clearly demonstrates that MS data-based fingerprinting is a meaningful tool not only in identifying constituents in complex matrix but also in directly screening for powerful trace ingredients in natural products.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Wanga
authors.forename: Qingxin
authors.initials: Q
authors.lastname: Cui
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Hou
authors.forename: Fang
authors.initials: F
authors.lastname: Bai
authors.forename: Jixue
authors.initials: J
authors.lastname: Sun
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Cao
authors.forename: Pi
authors.initials: P
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.forename: Gang
authors.initials: G
authors.lastname: Bai
mesh_terms: D020134:Catalytic Domain; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004791:Enzyme Inhibitors / Q000032:analysis*; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D008958:Models, Molecular; D009844:Oligosaccharides / Q000737:chemistry* / Q000494:pharmacology; D000516:alpha-Amylases / Q000037:antagonists & inhibitors
chemical_list: D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D009844:Oligosaccharides; D000516:alpha-Amylases