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The electron-rich five-membered aromatic aza-heterocyclic imidazole, which contains two nitrogen atoms, is an important functional fragment widely present in a large number of biomolecules and medicinal drugs; its unique structure is beneficial to easily bind with various inorganic or organic ions and molecules through noncovalent interactions to form a variety of supramolecular complexes with broad medicinal potential, which is being paid an increasing amount of attention regarding more and more contributions to imidazole-based supramolecular complexes for possible medicinal application. This work gives systematical and comprehensive insights into medicinal research on imidazole-based supramolecular complexes, including anticancer, antibacterial, antifungal, antiparasitic, antidiabetic, antihypertensive, and anti-inflammatory aspects as well as ion receptors, imaging agents, and pathologic probes. The new trend of the foreseeable research in the near future toward imidazole-based supramolecular medicinal chemistry is also prospected. It is hoped that this work provides beneficial help for the rational design of imidazole-based drug molecules and supramolecular medicinal agents and more effective diagnostic agents and pathological probes. [ABSTRACT FROM AUTHOR]

Unique benzopyridone cyanoacetates (BCs) as new type of promising broad-spectrum antibacterial candidates were discovered with large potential to combat the lethal multidrug-resistant bacterial infections. Many prepared BCs showed broad antibacterial spectrum with low MIC values against the tested strains. Some highly active BCs exhibited rapid sterilization capacity, low resistant trend and good predictive pharmacokinetic properties. Furthermore, the highly active sodium BCs (NaBCs) displayed low hemolysis and cytotoxicity, and especially octyl NaBC 5g also showed in vivo potent anti-infective potential and appreciable pharmacokinetic profiles. A series of preliminary mechanistic explorations indicated that these active BCs could effectively eliminate bacterial biofilm and destroy membrane integrity, thus resulting in the leakage of bacterial cytoplasm. Moreover, their unique structures might further bind to intracellular DNA, DNA gyrase and topoisomerase IV through various direct noncovalent interactions to hinder bacterial reproduction. Meanwhile, the active BCs also induced bacterial oxidative stress and metabolic disturbance, thereby accelerating bacterial apoptosis. These results provided a bright hope for benzopyridone cyanoacetates as potential novel multitargeting broad-spectrum antibacterial candidates to conquer drug resistance. [Display omitted] • Benzopyridone cyanoacetates as new broad-spectrum antibacterials were discovered. • Active compounds exerted potent bioactivity with low MICs of 0.25–0.5 μg/mL against most of the tested bacteria. • Active compounds displayed rapidly sterilization ability, low resistance trend and low hemolysis and cytotoxicity. • Compound 5g showed anti-infective potential and appreciable pharmacokinetic profiles in vivo. • Active compounds could destroy bacterial membrane, intercalate into DNA and induce cellular imbalance. [ABSTRACT FROM AUTHOR]

[Display omitted] In an effort for fighting with dreadful drug resistance, iminotetraberberine was hybridized with metronidazole to construct a unique type of potential broad-spectrum antibacterial iminotetrahydroberberine-corbelled metronidazoles. Some prepared hybrids exerted promising inhibitory effects against the tested microorganisms in comparison to the natural berberine, clinical metronidazole and norfloxacin. Noticeably, phenyl oxime derivative 8e displayed a broad antibacterial spectrum with a quite low MIC value of 0.024 mM against P. aeruginosa , being 63-, 62- and 2-fold to berberine, metronidazole and norfloxacin, respectively. The active compound 8e with low cytotoxicity under effective bacteriostatic concentration could decrease biofilm viability and show much lower trend to induce the resistant development than norfloxacin in the tested period. Mechanism investigation showed that compound 8e could disturb the bacterial membrane to lead to the leakage of cellular contents, thus exerting potent antibacterial potency. It was also revealed that compound 8e could interact with penicillin binding protein via multi-site non-covalent binding in docking simulation. The above results manifested that iminotetrahydroberberine-corbelled metronidazoles might bring hope for the exploitation of new broad-spectrum antibacterial agents with a membrane-destruction mechanism. [ABSTRACT FROM AUTHOR]

[Display omitted] Pyrimidine-conjugated fluoroquinolones were constructed to cope with the dreadful resistance. Most of the target pyrimidine derivatives effectively suppressed the growth of the tested strains, especially, 4-aminopyrimidinyl compound 1c showed a broad antibacterial spectrum and low cytotoxicity and exhibited superior antibacterial potency against Enterococcus faecalis with a low MIC of 0.25 μg/mL to norfloxacin and ciprofloxacin. The active compound 1c with fast bactericidal potency could inhibit the formation of biofilms and showed much lower trend for the development of drug-resistance than norfloxacin and ciprofloxacin. Further exploration revealed that compound 1c could prompt ROS accumulations in bacterial cells and interact with DNA to form a DNA- 1c complex, thus facilitating bacterial death. ADME analysis indicated that compound 1c possessed favorable drug-likeness and promising pharmacokinetic properties. These results demonstrated that pyrimidine-conjugated fluoroquinolones held hope as potential antibacterial candidates and deserve further study. [ABSTRACT FROM AUTHOR]