Latest ArticlesPolymyxin B (PB), as the last-line of defense against multidrug-resistant Gram-negative bacteria, has caused resistance to P. aeruginosa recently. Fortunately, synergistic treatment could preserve the last class of antibiotics and reduce the emergency of drug resistance. Here, we performed a screen of 970 approved drugs synergized with PB against the P. aeruginosa DK2, which is severely resistant to PB, MIC = 512 μg/mL. Encouragingly, we found fluoroquinolones could synergy with PB and achieved an obvious reduction in MIC of PB below the clinical susceptible breakpoint (2 μg/mL). Especially, gemifloxacin achieved the highest synergistic effect with PB, leading to a 4096-fold MIC reduction (reduced from 512 μg/mL to 0.125 μg/mL). Furthermore, synergistic effect was also observed in the combination of gemifloxacin and colistin. Finally, outer membrane permeabilization assay showed that gemifloxacin could increase the permeability of bacterial cell membranes for P. aeruginosa which partly explained the synergy mechanism. These results indicate that fluoroquinolones represent attractive synergists to address the emerging threat of polymyxin-resistant infections.
X-ray imaging functionalization of biodegradable polyesters is a great demand and challenge in biomedical applications. In this work, a strategy of in-chain functionalization through the combination of ring opening copolymerization and oxime "Click" postfunctionalization was developed towards X-ray opaque polylactide copolymers. A functionalized cyclic carbonate was first synthesized and used as comonomer of polylactide copolymers, which were subjected to postfunctionalization of oxime "Click" reaction towards iodinated polylactide copolymers. The chemical structure and physical properties of the target products were traced and confirmed. In vitro cytotoxicity evaluation with 3T3-Swiss albino by Alamar blue demonstrated a low cytotoxicity. The X-ray radiopacity was analyzed by Micro-CT and quantified by Hounsfield Units value, which could be tailorable by the feedstock. It is a promising X-ray visible implantable biomaterial in biomedical applications.
In this work, a multi-functional analysis platform by coupling a microfluidic chip to a mass spectrometry (MS) detector was described. We constructed a three-dimensional tumor-endothelial co-culture model for simulating drug resistance during tumor treatment. On this specially designed integrated platform, the first step was to prepare heterogeneous cell-encapsulated alginate microcapsules for threedimensional co-culture, and the second step was to achieve on-line perfusion culture and continuous drug stimulation on chip. It facilitates cell proliferation analysis and the collection of metabolism medium. After micro solid phase extraction column (SPE) pretreatment, subsequent mass spectrometry could detect drug metabolism. The high activity of two kinds of cells (A549 and HUVEC) shows the biocompatibility of the platform. Paclitaxel was used as a model drug, the distinctions of drug absorption between the mono-culture group and co-culture group were clearly observed by electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF MS). Therefore, the integrated platform has shown promise as a high throughput, low cost for cell metabolism research and drug screening processes.
In this study, we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors. MTT assays indicated that most of the compounds significantly inhibited multiple cancer cells proliferation. In addition, all the compounds displayed Topo Ⅱ inhibition activity at 10 mol/L, and also possessed good PARP-1 inhibitory activities. Subsequent mechanistic studies showed that compound 9a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 cells. Our study suggested that 9a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy.
Here, a new designed core/satellite gold nanoprobe was developed for detecting trace mount of benzoyl peroxide (BPO) based on its deboronation. This gold nanoassembly (the BE-AuNPs12/65) was constructed via borate ester formation between large 4-mercaptophenylboronic acid (MPBA) modified AuNPs (the MPBA-AuNPs65, as cores)and smalldopamine modifiedAuNPs (theDPA-AuNPs12, assatellites).Particularly, upon addition of BPO, it would trigger the deboronation for the BE-AuNPs12/65 probes accompanying with distinct color changes from blue, purple to wine red, which implied the disassembly of the core/satellite nanostructure after the breakage of carbon to boron chemical bond. By measuring the absorbance ratio at 665 nm and 545 nm, quantification of BPO was achieved in the range of 10.0-100.0 nmol/L, which could also be easilyobserved bynaked eyes. The nanoprobeutilized a boronate deprotection mechanism and the LSPR properties of AuNPs to provide high selectivity for detecting BPO over similar ROS/RNS with the limit of detection as low as 7.2 nmol/L. The practical applicability of this assay was verified through successful determining BPO in flour samples, which demonstrated its great potentials in food safety field.
A novel meroterpenoid, euphoractone (1), was isolated from the extracts of the roots of Euphorbia fischeriana Steud. Its structure was determined by spectroscopic methods and X-ray crystallography. 1 possesses an unusual ent-abietane-phloroglucinol skeleton. The plausible biosynthetic pathway for 1 was proposed.1 showed inhibitory activities against human lung cancer H23 and H460 cells with the IC50 values of 21.07±3.54 and 20.91±4.07 μmol/L.
A series of structurally novel 1, 3, 4-oxadiazole thioether derivatives (6a-6z) containing a 6-fluoroquinazolinylpiperidinyl moiety were designed and synthesized using pharmacophore hybrid approach, and their structures were fully characterized by 1H NMR, 13C NMR and HRMS spectra. Among them, the structure of compound 6d was further corroborated via single-crystal X-ray diffraction analysis. In vitro antibacterial bioassays showed that compounds 6a, 6g, 6u and 6v possessed EC50 values of 30.4, 30.6, 27.5 and 26.0 μg/mL against phytopathogenic bacterium Xanthomonas oryzae pv. oryzae, respectively, which were significantly superior to that of commercially-available bactericide Bismerthiazol (85.1 μg/mL). Moreover, in vitro antifungal bioassays indicated that seven compounds demonstrated broad-spectrum fungicidal acitivties against six types of phytopathogenic fungi at 50 μg/mL. The present work showed the potential of 1, 3, 4-oxadiazole thioether derivatives carrying a 6-fluoroquinazolinylpiperidinyl moiety as effective antimicrobial agents for crop protection, deserving further investigations in the future.
Enantiomerically pure 2-substituted indolines are an important class of nitrogen heterocycles that occur frequently in many alkaloid natural products and biologically active compounds. Consequently, the synthesis of such skeletons is of great significance. The past years have witnessed a number of remarkable advances in the development of efficient strategies to construct this class of chiral compounds. This review summarizes the recent advances in asymmetric synthesis of 2-substituted indoline derivatives. Due to the limitation of the length, this review only summarizes those works published from January of 2012 to January of 2019. Meanwhile, methods towards synthesis of fused and spirocyclic indolines will not be discussed in this review.
As a kind of stimuli-responsive materials, the disulfide-containing material has received a tremendous amount of interest. A novel functional disulfide-containing waterborne polyurethane (DS-WPU) nanoemulsion was prepared via a one-step in situ phase inverse emulsification technique and its reducing-responsive property was investigated using dithiothreitol as the reductant. Results showed that the DS-WPU nanoemulsion had a uniform particle size in nanoscale and a good film-forming characteristic, and the DS-WPU latex film exhibited great responsiveness along with a self-assembled behavior in the reducing environment to form WPU emulsion again, including a long-to-short process of the polymer chains.
Design and development of iron porphyrin-based artificial enzymes system have been attracting a lot of attention. Herein, without any toxic reductant and harsh processing, we present a facile one-pot method to fabricate bifunctional catalytic nanocomposites consisting of graphene and hemin by using vitamin C as a mild reduction reagent. The presence of graphene helps the formation of a high degree of highly active and stable hemin on the graphene surface in a monomeric form through their π-π stacking interaction. As a result, such nanocomposites possess a superior adsorption capacity and intrinsic peroxidase-like catalytic activity. Moreover, by the combination of their dye adsorption ability, RGOhemin nanocomposites can serve as a suitable candidate for efficient capture and removal of dyes via a synergistic effect. Our findings may pave the way to apply graphene-supported artificial enzymes in a variety of fields, such as environmental chemistry, bionics, medicine, and biotechnology
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