Hui-Zhen Zhang

Synthesis of tetrazole compounds as a novel type of potential antimicrobial agents and their synergistic effects with clinical drugs and interactions with calf thymus DNA

A series of tetrazole derivatives were synthesized and characterized by NMR, IR, MS and HRMS spectroscopy. The bioactive assay manifested that most of the target compounds exhibited good antifungal activity, especially compound 6g displayed comparable or even stronger antifungal efficiency in comparison with the reference drug Fluconazole. The combination of tetrazole derivative 6g with antibacterials Chloromycin and Norfloxacin, or antifungal Fluconazole respectively was more sensitive to methicillin-resistant MRSA and Fluconazole-insensitive Aspergillus flavus. Further research revealed that compound 6g could effectively intercalate into Calf Thymus DNA to form a 6g–DNA complex which might block DNA replication to exert its good antimicrobial activities.

Design, synthesis, and biological evaluation of novel benzimidazole derivatives and their interaction with calf thymus DNA and synergistic effects with clinical drugs

A series of new benzimidazole derivatives was synthesized and characterized by IR, 1H NMR, 13C NMR, MS, and HRMS spectra. All the new compounds were screened for their antimicrobial activities in vitro by a twofold serial dilution technique. The bioactive evaluation showed that 3,5-bis(trifluoromethyl)phenyl benzimidazoles were comparably or even more strongly antibacterial and antifungal than the reference drugs Chloromycin, Norfloxacin, and Fluconazole. The combination of 2,4-difluorobenzyl benzimidazole derivative 5l and its hydrochloride 7 respectively with the antibacterials Chloromycin, Norfloxacin, and the antifungal Fluconazole was more sensitive to methicillin-resistant MRSA and Fluconazole-insensitive A. flavus. In addition, the interaction of compound 5l with calf thymus DNA demonstrated that this compound could effectively intercalate into DNA to form a compound 5l-DNA complex that might block DNA replication and thereby exert good antimicrobial activity.

Current developments in the syntheses of 1,2,4-triazole compounds

Heterocyclic 1,2,4-triazole derivatives possess unusually spacious potentiality as medicinal agents, agricultural chemicals, functional materials, ionic liquids, supramolecular catalysts as well as artificial enzymes and receptors for supramolecular recognition and biomimetic catalysis, and their various researches and developments have been being a quite rapidly developing and active highlight topic with an infinite space. Numerous efforts have been directed toward various types of possible applications of 1,2,4-triazole-based compounds and a lot of important progress has been made, especially their preparations have attracted increasing attention. This review systematically summarized the recent advances in the syntheses of 1,2,4-triazole derivatives, including: (1) Cyclizations to form triazole ring; (2) Transformations of heterocyclic compounds to construct triazole ring; (3) Substitutions on 1,2,4-triazole ring; (4) Structural modifications in side chains of 1,2,4-triazole ring. It was hoped that this review would be helpful for the design and development of highly efficient preparation of 1,2,4-triazole derivatives with various sorts and varieties of extensively potential applications in medicine, agriculture, chemistry, materials, supramolecular sciences and so on.

Design, synthesis and antimicrobial evaluation of novel benzimidazole-incorporated sulfonamide analogues

A novel series of benzimidazole-incorporated sulfonamide analogues were designed and synthesized with an effort to overcome the increasing antibiotic resistance. Compound 5c gave potent activities against Gram-positive bacteria and fungi, and 2,4-dichlorobenzyl derivative 5g showed good activities against Gram-negative bacteria. Both of these two active molecules 5c and 5g could effectively intercalate into calf thymus DNA to form compound-DNA complex respectively, which might block DNA replication to exert their powerful antimicrobial activity. Molecular docking experiments suggested that compounds 5c and 5g could insert into base-pairs of DNA hexamer duplex by the formation of hydrogen bonds with guanine of DNA. The transportation behavior of these highly active compounds by human serum albumin (HSA) demonstrated that the electrostatic interactions played major roles in the strong association of active compounds with HSA, and which was also confirmed by the full geometry calculation optimizations.

New Progress in Azole Compounds as Antimicrobial Agents

The increasing incidence of microbial resistance and newly emerging pathogens have become a serious challenge for public health. More and more efforts have been directed to the development of new antimicrobial agents with distinct mechanisms from the well-known classes of clinical drugs. The extensive clinical utilization of azole-based medicinal drugs has evoked numerous attentions, and their researches and developments have been a quite rapid developing and active highlight topic with an infinite space. Consideration of our researches on azole compounds and other literature in recent three years, this review scientifically reviewed the new progress of azole derivatives as antibacterial, antifungal, antitubercular and antiviral agents, including mono-nitrogen azoles (oxazoles, thiazoles and carbazoles), bis-nitrogen azoles (imidazoles, pyrazoles and benzimidazoles) and tri-nitrogen azoles (triazoles and benzotriazoles) as well as tetrazole derivatives. It was hoped that this review would be helpful for the design and development of highly efficient azole derivatives with high bioactivity and low toxicity.

Synthesis of novel sulfonamide azoles via C–N cleavage of sulfonamides by azole ring and relational antimicrobial study

A series of novel sulfonamide azoles were synthesized via C–N cleavage of sulfonamides by an azole ring. This type of reaction could be performed smoothly in DMF and some influential factors including temperature, solvent and reaction time to this reaction were also investigated. The antimicrobial results revealed that sulfonamide 9d bearing a 2-methyl-5-nitroimidazole moiety gave the best anti-P. aeruginosa efficiency in this series and was equivalent to chloromycin (MIC = 16 μg mL−1). The combination of sulfonamide azole 9d with chloromycin, norfloxacin, or fluconazole gave significant synergistic effects. Further research showed that compound 9d could effectively intercalate into calf thymus DNA to form the 9d–DNA complex, which might block DNA replication to exert its powerful antimicrobial activity. The transportation behavior of this compound using human serum albumin (HSA) demonstrated that the electrostatic interactions played major roles in the strong association of compound 9d with HSA.