Upon single treatment against Staphylococus aureus, quercetin-pivaloxymethyl conjugate (Q-POM) had antibacterial activities with minimum inhibitory concentrations (MICs) of 16-32 mg/L. Q-POM showed MIC of 32 mg/L against vancomycin-resistant Enterococcus faceium (VRE), which is remarkably lower than other antibiotics investigated (≥256 mg/L). Under sub-MIC concentrations, Q-POM potentiated the activity of ampicillin, cefepime, and vancomycin against S. aureus and Enterococcus (including highly resistant strains such as hetero-resistant vancomycin-intermediate S. aureus (hVISA), vancomycin-intermediate S. aureus (VISA), and VRE), by decreasing the MICs of these antibiotics by 4-128 folds. Q-POM was found to be partially synergistic with ampicillin and cefepime against S. aureus and Enterococcus, while it was strongly synergistic with vancomycin. Q-POM at 5 mg/L inhibited the formation of biofilms of S. aureus by 24-83% and VRE by 70%. Additionally, Q-POM inhibited the hemolytic activity of S. aureus in a dose-dependent manner. Cytotoxic activity was evaluated in human liver epithelial cells (HepG2), and the 50% cytotoxicity concentration (CC 50) value of Q-POM was higher than 50 mg/L. These results indicate the potential use of Q-POM in treatment of methicillin-resistant Staphylococcus aureus (MRSA) and VRE infections.

Investigations into tau-targeting diagnosis of Alzheimer's disease are currently underway, and the development of tau-selective molecular probes is urgently required. In this study, the donor-π-acceptor architecture of the previously reported tau-selective fluorescence probe was modified into thiophene-π-cyanoacetamides. While the fluorescence properties of the prepared probes were not influenced by the thiophene substituents, intense and tau-selective turn-on fluorescence in the near infrared region was observed only in the probes with unsubstituted phenyl or p-methylphenyl cyanoacetamides in the acceptor functionality. Compared with the parent compound, the newly identified probes showed 1.5 $ 4.1 times increase in tau-selectivity over Aβ fibrils and 3.5 $ 4.7 times increase in fluorescence intensity. The tau-selective fluorescence properties of the title probes were further demonstrated in the cellular milieu, and the green and red fluorescence emitted by GFP and tau-bound probes, respectively, were shown to be nicely colocalized in the SH-SY5Y cells stably expressing GFP-tagged tau.

Based on the observations suggesting that a digallate functionality might serve as a novel scaffold for inducers of mitochondrial biogenesis, we prepared a series of digallates and evaluated their activity in an in vitro model widely used in PD research (SH-SY5Y cells). Flow cytometry-based approach revealed stimulation of mitochondrial biogenesis by the gallates, particularly by those with the gallate substituted at the 1,2-or 1,3-positions. The relative mitochondrial mass calculated after taking cell sizes into account also confirmed the 1,2-or 1,3-digallates as stimulators of mitochondrial biogenesis. Finally, energy sensing network including AMPK, SIRT1, and PGC-1α was shown to be affected by 1,2-or 1,3-digallates to stimulate mitochondrial biogenesis. Taken together, this study presents a 1,2-or 1,3-digallate as a novel scaffold for stimulators of mitochondrial biogenesis. As inducers of mitochondrial biogenesis remain scarce, the current findings provide a valuable tool in the battle against neurodegenerative diseases.

Escherichia coli harboring Os4CL and OsHCT4 was used to synthesize (S)‐p‐coumaroyl glycerol.

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