Imidazole ring is an important five‐membered aromatic heterocycle widely present in natural products and synthetic molecules. The unique structural feature of imidazole ring with desirable ...electron‐rich characteristic is beneficial for imidazole derivatives to readily bind with a variety of enzymes and receptors in biological systems through diverse weak interactions, thereby exhibiting broad bioactivities. The related research and developments of imidazole‐based medicinal chemistry have become a rapidly developing and increasingly active topic. Particularly, numerous imidazole‐based compounds as clinical drugs have been extensively used in the clinic to treat various types of diseases with high therapeutic potency, which have shown the enormous development value. This work systematically gives a comprehensive review in current developments of imidazole‐based compounds in the whole range of medicinal chemistry as anticancer, antifungal, antibacterial, antitubercular, anti‐inflammatory, antineuropathic, antihypertensive, antihistaminic, antiparasitic, antiobesity, antiviral, and other medicinal agents, together with their potential applications in diagnostics and pathology. It is hoped that this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic imidazole‐based medicinal drugs, as well as more effective diagnostic agents and pathologic probes.
Coumarin compounds represent an important type of naturally occurring and synthetic oxygen-containing heterocycles with typical benzopyrone framework. This type of special benzopyrone structure ...enables its derivatives readily interact with a diversity of enzymes and receptors in organisms through weak bond interactions, thereby exhibit wide potentiality as medicinal drugs. So far, some coumarin-based drugs such as anticoagulant and antineurodegenerative agents have been extensively used in clinic. Coumarin-containing supramolecular medicinal agents as a new increasing expansion of supramolecular chemistry in pharmaceutical science have also been actively investigated in recent years. Coumarin-derived artificial ion receptors, fluorescent probes and biological stains are growing quickly and have a variety of potential applications in monitoring timely enzyme activity, complex biological events as well as accurate pharmacological and pharmacokinetic properties. This review provides a systematic summary and insight of the whole range of medicinal chemistry in the current developments of coumarin compounds as anticoagulant, antineurodegenerative, anticancer, antioxidative, antibacterial, antifungal, antiviral, antiparasitic, antiinflammatory and analgesic, antidiabetic, antidepressive and other bioactive agents as well as supramolecular medicinal drugs, diagnostic agents and pathologic probes, and biological stains. Some rational design strategies, structure-activity relationships and action mechanisms are discussed. The perspectives of the future development of coumarinbased medicinal chemistry are also presented.
IMPORTANCE: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of ...relapse and death are needed. OBJECTIVE: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy. INTERVENTIONS: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. MAIN OUTCOMES AND MEASURES: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events. RESULTS: Among 443 women who were randomized, 434 were included in the full analysis set (mean SD age, 46 9.9 years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio HR for risk of recurrence or death, 0.64 95% CI, 0.42-0.95; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 95% CI, 0.38-0.92; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 95% CI, 0.47-1.19; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 95% CI, 0.46-1.13; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event. CONCLUSIONS AND RELEVANCE: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01112826
Unique coumarin aminophosphonates as new antibacterial agents were designed and synthesized to combat severely bacterial resistance. Bioactivity assessment identified that 3-hydroxylphenyl ...aminophosphonate 6f with low hemolytic activity not only exhibited excellent inhibition potency against Staphylococcus aureus at low concentration (0.5 μg/mL) in vitro but also showed considerable antibacterial potency in vivo. Meanwhile, the active compound 6f was capable of eradicating the S. aureus biofilm, thus alleviating the development of S. aureus resistance. Furthermore, the drug combination of compound 6f with norfloxacin could enhance the antibacterial efficacy. Mechanistic explorations manifested that molecule 6f was able to destroy the integrity of cell membrane, which resulted in the leakage of protein and metabolism inhibition. The cellular redox homeostasis was interfered through inducing the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), leading to the reduction of glutathione (GSH) activity and lipid peroxidation. Furthermore, compound 6f could intercalate into DNA base pair to hinder normal biological function. The above results provided powerful information for the further development of coumarin aminophosphonates as antibacterial agents.
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•Unique coumarin aminophosphonates with potent antibacterial efficacy were developed.•Molecule 6f exerted low toxicity, no obvious resistance and good bioavailability.•Compound 6f could disturb the membrane integrity and lead to the leakage of intracellular materials.•Compound 6f could induce oxidative damage and restrain metabolism.
Polymers of intrinsic microporosity are attractive membrane materials for gas separation due to their high specific surface and microporous structure. PIM-1 being the most representative one shows ...extremely high permeability but moderate selectivity for CO2 separation. In this study, the CO2 selectivity of PIM-1 is remarkably enhanced via blending with polyethylene glycol (PEG). A series of PIM-1/PEG blended membranes are prepared for separation of CO2/N2, CO2/CH4 by varying the molecular weight (MW) and content of PEG. Their structure and physicochemical properties are explicitly characterized including density, morphology and thermostability. The blended membranes have less d-spacing of packed chains than pure PIM-1. The pure gas permeabilities of CO2, N2 and CH4 are measured with varying MW and content of PEG. The PEG blend depresses gas permeability of the PIM-1 membrane but greatly improves the CO2 selectivity, especially for CO2/CH4 separation. The membranes with 2.5wt% PEG at different MWs have excellent separation performance for CO2/CH4 separation, which surmounts the 2008 upper bound line. Specifically the membrane with 3.5wt% PEG of 20kDa has the CO2 permeability of 1952 barrer and CO2/CH4 selectivity of 39.0 that is more than three times that of the pure PIM-1 membrane. The as-prepared PIM-1/PEG membranes have a great potential for CO2 separation.
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•The blended membranes are prepared by varying molecular weight and content of PEG.•The introduction of PEG adjusts structure and properties of the PIM-1 membrane.•The PEG blend greatly enhances the CO2 selectivity of the PIM-1 membrane.•The separation performance for CO2/CH4 surpasses the 2008 upper bound line.•The blended membranes exhibit a great potential application in CO2 separation.
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•Strategies towards enhanced performance of zeolite catalysts were evaluated.•Accessibility of large molecules is improved through raising Deff or lowering L.•Active sites located ...inside the micropores control the catalytic performance.
In the present study, two strategies for improving the catalyst efficiency either by (1) raising the effective diffusion coefficient or (2) reducing the diffusion length of zeolite catalysts are presented. These two strategies are exemplified by the preparation of (i) ordered mesoporous material with zeotype secondary building units and (ii) self-assembled nanosized zeolites. The textural properties, acidity, and the results from the cumene cracking show that the strength and amount of Brønsted acid sites of the mesoporous materials are inferior, due to their amorphous pore walls. Even though the lifespan of ordered mesoporous material with zeotype secondary building units during cumene cracking can be improved due to the effective diffusion coefficient enhancement, the strength and amount of Brønsted acid sites related to the reaction are not akin to conventional microporous zeolites. While the self-assembled nanosized zeolites with short diffusion length shows enhanced catalytic performance by diffusion controlled reactions.
A new type of benzopyrone-mediated quinolones (BMQs) was rationally designed and efficiently synthesized as novel potential antibacterial molecules to overcome the global increasingly serious drug ...resistance. Some synthesized BMQs effectively suppressed the growth of the tested strains, outperforming clinical drugs. Notably, ethylidene-derived BMQ 17a exhibited superior antibacterial potential with low MICs of 0.5–2 μg/mL to clinical drugs norfloxacin, it not only displayed rapid bactericidal performance and inhibited bacterial biofilm formation, but also showed low toxicity toward human red blood cells and normal MDA-kb2 cells. Mechanistic investigation demonstrated that BMQ 17a could effectually induce bacterial metabolic disorders and promote the enhancement of reactive oxygen species to disrupt the bacterial antioxidant defense system. It was found that the active molecule BMQ 17a could not only form supramolecular complex with lactate dehydrogenase, which disturbed the biological functions, but also effectively embed into calf thymus DNA, thus affecting the normal function of DNA and achieving cell death. This work would provide an insight into developing new molecules to reduce drug resistance and expand antibacterial spectrum.
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•New benzopyrone-mediated quinolones with broad antimicrobial spectrum were developed.•Compound 17a exerted more potent inhibition efficacy with low MICs of 0.5–2 μg/mL than the reference drug norfloxacin.•Compound 17a showed low toxicity and no obvious resistance.•Compound 17a could effectively decrease the glutathione activities and promote the production of ROS.•Compound 17a could form 17a–DNA complex by intercalation, thus leading to bacterial death.
We introduced a strategy for preparing a carbohydrate microarray and demonstrated its utility for characterizing carbohydrate binding and activities. We isolated the lipopolysaccharide (LPS) ...components from different bacteria and explored the possibility of immobilizing these glycoconjugates on a high-binding polystyrene plate. Carbohydrate-specific combination was examined by observing the binding of the blood group B analogic LPS
O
-polysaccharide from
Escherichia coli
on the high-binding polystyrene plate and anti-B from a broad spectra antibody of human blood serum. Strong binding of antibodies was screened, as it was evident that relative response value is two times higher than control. The hybridization results indicated that this method is a reliable technique for the detection of human intestinal bacteria and is expected to be applied in diagnostics and seroepidemiology.
Lead halide perovskites have received increasing attention recently as a candidate material in various optoelectronic areas because of their high performance as light absorbers. Herein, we report the ...growth of CsPbI
3
nanobelts via a solution process. A single-crystalline CsPbI
3
nanobelt with uniform morphology can be achieved by controlling the amount of PbI
2
. A single-crystalline CsPbI
3
nanobelt possesses a mean width, length, and thickness of 100 nm, 5 µm, and 20 nm, respectively. In this work, photodetectors (PDs) based on individual CsPbI
3
nanobelts are constructed and found to perform well with an external quantum efficiency and responsivity of 2.39 × 10
5
% and 770 A/W, respectively. The PDs also show a high detectivity of up to 3.12 × 10
12
Jones, which is at par with that of Si PDs. The PDs developed in this work exhibit great promise in various optoelectronic nanodevices.
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