Limin Wang,Yunsen Zhang,I. Agbaka Johnpaul,Kai Hong,Hanlu Gao,Yumei Song,Chenyan Lv,Changwei Ma
Xanthohumol (XN), as an abundant chalcone in hops, has received increasing attention due to its pharmacologic effects. However, poor solubility and bioaccessibility in aqueous solutions have limited its application. This work reported a novel carrier to improve the solubility and bioaccessibility of XN by using heat-stable, serpin-like protein Z (PZ) derived from barley malt. In this study, the solubility of XN was increased by 145-fold (vs. free XN in water) using 200 μM PZ as the carrier. Fluorescence results demonstrated that XN interacted with PZ via static quenching process, with binding constant (K a ) of 5.70 × 10 4 L/mol at 298 K. PZ as a serine protease inhibitor exhibited excellent in vitro digestive stability that could inhibit trypsin with a low half inhibitory concentration (IC 50 ) of 3.90 ± 0.03 mg/L and showed only 26.54 ± 0.70% degree of hydrolysis after gastrointestinal digestion. Furthermore, the retention ratio of XN was 50.28 ± 1.80% after gastrointestinal digestion, which is 8-fold higher than XN alone, suggesting that PZ remarkably enhanced the bioaccessibility of XN. Molecular dynamics simulation analysis revealed that XN was bound within the hydrophobic pocket of PZ, near the Glu338 residue of PZ, whereas the external active loop of PZ was involved in binding with trypsin. This helped to elucidate the roles of PZ in improving the bioaccessibility of XN that PZ encapsulated XN in its hydrophobic cavity, without influencing its inhibition on trypsin. These findings suggest that PZ may be developed as carriers that protect XN or other hydrophobic bioactive molecules in the gastrointestinal tract.
Xanthomonas oryzae pv. oryzae (Xoo) is an offensive phytopathogen that can invade a wide range of plant hosts to develop bacterial diseases, including the well-known rice bacterial leaf blight. However, few agrochemicals have been identified to effectively prevent and eliminate Xoo-induced diseases. Thus, designing novel antibacterial compounds on the basis of the potential targets from Xoo may lead to the discovery of highly efficient and innovative anti-Xoo agents. Filamentous temperature-sensitive protein Z (FtsZ), an important functional protein in the progression of cell division, has been widely reported and exploited as a target for creating antibacterial drugs in the field of medicine. Therefore, the fabrication of innovative frameworks targeting XooFtsZ may be an effective method for managing bacterial leaf blight diseases via blocking the binary division and reproduction of Xoo. As such, a series of novel N-(cinnamoyl)-N′-(substituted)acryloyl hydrazide derivatives containing pyridinium moieties were designed, and the anti-Xoo activity was determined. The bioassay results showed that compound A7 had excellent anti-Xoo activity (EC50 = 0.99 mg L–1) in vitro and distinct curative activity (63.2% at 200 mg L–1) in vivo. Further studies revealed that these designed compounds were XooFtsZ inhibitors, validating by the reduced GTPase activity of recombinant XooFtsZ, the nonfilamentous XooFtsZ assembly observed in the TEM images, and the prolonged Xoo cells from the fluorescence patterns. Computational docking studies showed that compound A7 had strong interactions with ASN34, GLN193, and GLN197 residues located in the α helix regions of XooFtsZ. The present study demonstrates the developed FtsZ inhibitors can serve as agents to control Xoo-induced infections.
危险品化学品经营许可证（带存储）