Zhou Cheng-He

Comprehensive review in current developments of imidazole-based medicinal chemistry (该论文成为ESI论文，并被评为 2014年度“中国百篇最具影响国际学术论文”)

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.

Recent advances in the researches of triazole compounds as medicinal drugs

Triazole compounds as medicinal drugs are extensively used in clinic, and are currently one of the most important fields in the researches and developments of drugs. More and more triazole compounds, with strong pharmacological activity, low toxicity, less adverse effects, fewer multi-drug resistances, high bioavailability, good pharmacokinetics property and drug-targeting, diversity of drug administration, broad spectrum, better curative effect etc. are frequently employed as candidates or clinical drugs for the therapy of various types of diseases, which have showed their large development value and wide potential as medicinal agents. Combining with authors researches and referring other works from literatures in recent 5 years, this work systematically reviewed the new researches and developments of the whole range of triazole compounds as medicinal drugs for the first time, including antifungal, antibacterial, anti-tuberculosis, anticancer, antivirus, anti-inflammatory, anti-convulsion and so on. The perspectives of the foreseeable future in the research and development of triazole compounds as medicinal drugs are also presented.

A series of naphthalimide azoles: Design, synthesis and bioactive evaluation as potential antimicrobial agents

A series of naphthalimide azoles as potential antibacterial and antifungal agents were conveniently and efficiently synthesized starting from commercially available 6-bromobenzo[de]isochromene-1,3-dione. All the new compounds were characterized by NMR, IR, MS and HRMS spectra. Their antimicrobial activities were evaluated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi using two-fold serial dilution technique. The biological assay indicated that most of the prepared compounds exhibited inhibition to the tested strains. In particular, the triazolium derivatives not only gave higher efficacy than their corresponding precursory azoles, but also demonstrated comparable or even better potency than the reference drugs Chloromycin, Orbifloxacin and Fluconazole. Some factors including structural fragments, pH and ClogP values of the target molecules were also preliminarily discussed.

Synthesis and biological activities of thio-triazole derivatives as novel potential antibacterial and antifungal agents

A series of novel thio-triazole derivatives including thiols, thioethers and thiones as well as some corresponding triazolium compounds were conveniently and efficiently synthesized from commercially available halobenzyl halides and thiosemicarbazide. All the new compounds were characterized by 1H NMR, 13C NMR, FTIR, MS and HRMS spectra. Their antibacterial and antifungal activities in vitro were evaluated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi by two-fold serial dilution technique. The preliminary bioassay indicated that some prepared triazoles exhibited effective antibacterial and antifungal activities. Especially, 3,4-dichlorobenzyl triazole-thione and its triazolium derivatives displayed the most potent activities against all the tested strains.

Recent advances in application of thiazole compounds

Thiazole ring is an important five-member aromatic heterocycle with nitrogen and sulfur atoms. This special structure of thiazole ring endows its derivatives to exhibit wide potential application in chemical, pharmaceutical, biological and material scicences and so on, which show great development value and attract increasingly special attention. A large number of researches have been focusing on thiazole compounds, the progress have been rapidly developing, and become one of highly active topics in recent years. Combining with authors’ researches and referring to other works from literatures in recent five years, this work systematically reviewed the recent advances of the whole range of thiazole compounds in medicinal agents, agrochemicals, materials, biological stains and supramolecular chemistry.

Design and synthesis of quinazolinone imidazoles and their antibacterial and DNA-targeting investigation

The rising emergence of multidrug-resistant bacteria is becoming an increasingly serious threat to human health, therefore the development of structurally novel drugs has been an important topic worldwide to overcome drug-resistant strains. In this work, a series of novel acylhydrazone-bridged quinazolinone imidazoles were designed, synthesized and characterized by 1H NMR, 13C NMR and HRMS spectra. Bioactive assays showed that some target compounds exhibited significant antimicrobial potency. Especially, octadecyl derivative 6h and 4-fluorobenzyl derivative 7i showed 2.5 ~ 3.3 folds stronger activities against bacteria S. dysenteriae and E. coli DH52 than chloramphenicol, and 28 as well as 8.4 times higher efficacies toward fungus A. flavus than clinical drug fluconazole. The DNA-targeting preliminary exploration of highly active compound 7i by UV-Vis spectroscopy revealed that imidazole derivative 7i could intercalate into calf thymus DNA to form 7i -DNA supramolecular complex and thus block DNA replication to exert powerful antibacterial activities. Molecular docking study displayed that the active molecule 7i could form hydrogen bond with DNA base. This class of compounds as new type of specific anti- A. flavus and antibacterial drugs were worthy of being deeply investigated.

Construction of benzimidazole-fused dihydrobenzoxazoles via Cu-catalyzed tandem C–H functionalization

Benzimidazole-fused dihydrobenzoxazoles are an important class of complex heterocycles containing both nitrogen and oxygen as building blocks for materials and pharmaceuticals. Traditional synthetic method for the skeleton lacks of step economy. This article describes the tandem cyclization of 1 H -benzimidazole and 2-bromophenol catalyzed by copper(II) via N -arylation/sp2 C−H activation/C−O bond cyclization to construct benzimidazole-fused dihydrobenzoxazoles in one-pot. The reaction was carried out under an air atmosphere with simple reactive conditions and easy handling. In addition, other benzimidazole derivatives, as well as 2-iodophenol and 2-hydroxybenzeneboronic acid, are also suitable for this reaction. This transformation provides a convenient method to synthesize a series of benzimidazole-fused dihydrobenzoxazoles.

Preparation of thermoresponsive and easily functional polymer brushes and their thermoresponsive properties

Thermoresponsive materials have overwhelming development prospects because of their excellent properties and widely potential applications. The polymer brushes of poly(MEO2MA- co -OEGMA526) were prepared by the copolymerization of 2-(2-methoxyethoxy)ethyl methacrylate (MEO2MA) and poly(oligo(ethylene glycol) methacrylate) (OEGMA526) on the gold surface of QCM chip via supramolecular self-assembled monolayers (SAM) and surface initiated polymerization (SIP). The thermoresponsive properties of polymer brushes were investigated by changing the solution concentration of initiator ( χ Isol), the molar concentration of monomer OEGMA526 ( C 526) and the dry film thickness ( d ). Studies via quartz crystal microbalance (QCM) showed that the lower critical solution temperature (LCST) of thermoresponsive polymer brushes poly(MEO2MA- co -OEGMA526) ( χ Isol = 1%; C 526 = 5%; LCST = 34 ℃) was mainly determined by the C 526 while the d almost had no effect. Terminal hydroxyl groups on thermoresponsive polymer brushes provided an opening for functional applications verified by the binding experiment of grafted biotin and streptavidin. Thermoresponsive and easily functional polymer brushes provide a new possibility for the development of novel temperature sensitive materials.