Non-natural 2H-azirine-2-carboxylic acids: an expedient synthesis and antimicrobial activity

Non-natural 2H-azirine-2-carboxylic acids were obtained in high yields by FeCl₂-catalyzed isomerization of 5-chloroisoxazoles to azirine-2-carbonyl chlorides followed by their hydrolysis. The 3-aryl- and 3-heteroaryl-substituted acids are stable during prolonged storage, exhibit antibacterial activity against ESKAPE pathogens and show a low level of cytotoxicity.

A method for the synthesis of 2H-azirine-2-carboxylic acids with high antibacterial activity against ESKAPE pathogens and low cytotoxicity was developed.     

Investigations into the structure–activity relationship in gemini QACs based on biphenyl and oxydiphenyl linker

Eighteen novel gemini quaternary ammonium compounds were synthesized to examine the effect of linker nature, aliphatic chain length and their relative position on antibacterial and antifungal activity. The synthesized compounds showed strong bacteriostatic activity against a panel of both Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and two fungi. Some of these compounds exhibited a wider and more potent antimicrobial spectrum than commonly-used antiseptics, such as benzalkonium chloride (BAC), cetylpyridinium chloride (CPC), chlorhexidine digluconate (CHG) and octenidine dihydrochloride (OCT).

The synthesis and biological evaluations of new gemini QACs possessing high antibacterial and antifungal activity were performed.     

The discovery of penta-peptides inhibiting the activity of the formylglycine-generating enzyme and their potential antibacterial effects against Mycobacterium tuberculosis

The formylglycine-generating enzyme is a key regulator that converts sulfatase into an active form. Despite its key role in many diseases, enzyme activity inhibitors have not yet been reported. In this study, we investigated penta-peptide ligands for FGE activity inhibition and discovered two hit peptides. In addition, the lead peptides also showed potential antibacterial effects in a Mycobacterium tuberculosis model.

A penta-peptide, SMMMC, inhibits the activity of formylglycine-generating enzyme.     

Emergent antibacterial activity of N-(thiazol-2-yl)benzenesulfonamides in conjunction with cell-penetrating octaarginine

Hybrid antimicrobials that combine the effect of two or more agents represent a promising antibacterial therapeutic strategy. In this work, we have synthesized N-(4-(4-(methylsulfonyl)phenyl)-5-phenylthiazol-2-yl)benzenesulfonamide derivatives that combine thiazole and sulfonamide, groups with known antibacterial activity. These molecules are investigated for their antibacterial activity, in isolation and in complex with the cell-penetrating peptide octaarginine. Several of the synthesized compounds display potent antibacterial activity against both Gram-negative and Gram-positive bacteria. Compounds with 4-tert-butyl and 4-isopropyl substitutions exhibit attractive antibacterial activity against multiple strains. The isopropyl substituted derivative displays low MIC of 3.9 μg mL⁻¹ against S. aureus and A. xylosoxidans. The comparative antibacterial behaviour of drug–peptide complex, drug alone and peptide alone indicates a distinctive mode of action of the drug–peptide complex, that is not the simple sum total of its constituent components. Specificity of the drug–peptide complex is evident from comparison of antibacterial behaviour with a synthetic intermediate–peptide complex. The octaarginine–drug complex displays faster killing-kinetics towards bacterial cells, creates pores in the bacterial cell membranes and shows negligible haemolytic activity towards human RBCs. Our results demonstrate that mere attachment of a hydrophobic moiety to a cell penetrating peptide does not impart antibacterial activity to the resultant complex. Conversely, the work suggests distinctive modes of antibiotic activity of small molecules when used in conjunction with a cell penetrating peptide.

Hybrid antimicrobials that combine the effect of two or more agents represent a promising antibacterial therapeutic strategy.     

Fluorination in enhancing photoactivated antibacterial activity of Ru(ii) complexes with photo-labile ligands

Fluorination in enhancing photoactivated antibacterial activity of Ru(ii) complexes with photo-labile ligands was studied. Ru(ii) polypyridine complexes containing a di-fluorinated dppz (dipyrido[3,2-a:2′,3′-c]phenazine) or mono-trifluoromethylated dppz bidentate ligand and four pyridine monodentate ligands (complexes 3 and 4) were found to show potent photoactivated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and Escherichia coli (E. coli) in both normoxic and hypoxic conditions. The bactericidal effect of complexes 3 and 4 under hypoxic conditions may stem from the fluorine-containing Ru(ii) aqua species after photo-induced pyridine dissociation, and DNA may be the potential antibacterial target. Photosensitized singlet oxygen may also account for their antibacterial activity under normoxic conditions. Moreover, negligible hemolysis rates as well as low dark- and photo-cytotoxicity toward human normal liver cells (L-O2) were also observed for both complexes. Our work may provide new insights into the development of novel and efficient Ru(ii) complex based photoactivatable antibacterial agents against antibiotic-resistant bacteria.

Fluorination in the dppz ligand efficiently enhanced the photoactivated antibacterial activity of Ru(ii) complexes with photo-labile ligands against antibiotic-resistant bacteria both under normoxic and hypoxic conditions.     

Antibacterial coordination polymer hydrogels composed of silver(i)-PEGylated bisimidazolylbenzyl alcohol

Herein, antibacterial coordination polymer hydrogels were conveniently fabricated in water via coordination between silver nitrate and PEGylated bisimidazolylbenzyl alcohol (1a–c). These coordination polymer hydrogels exhibit much better antibacterial activity than silver nitrate against both Gram-negative and Gram-positive pathogens including multidrug-resistant pathogens. The coordination polymer Ag/1c with a long PEG chain (PEG1000) was demonstrated to be the most effective antibacterial material, and its minimum inhibition concentrations (MICs) could be as low as 15.2 times for common Staphylococcus aureus and 4.8 times for methicillin-resistant Staphylococcus aureus over that of silver nitrate. With improved antibacterial performance, easy preparation method, improved stability, sustained releasability, outstanding ductility and low cytotoxicity, the as-prepared coordination polymer hydrogels should find various potential applications such as in clinical burn and wound dressings, biofilms, bioadhesives, and coatings of biomedical materials.

Herein, antibacterial coordination polymer hydrogels were conveniently fabricated in water via coordination between silver nitrate and PEGylated bisimidazolylbenzyl alcohol (1a–c).     

Copper(ii) complexes with terpene derivatives of ethylenediamine: synthesis,and antibacterial,antifungal and antioxidant activity

The synthesis of new chiral copper(ii) complexes with terpene derivatives of ethylenediamine and the results of studying their antibacterial, antifungal and antioxidant activity in vitro are discussed. All studied copper complexes (1–4) showed significantly higher antifungal activity against the strains of C. albicans, S. salmonicolor and P. notatum compared to the activity of the clinical antifungal drug amphotericin. High antibacterial activity of copper complexes with terpene derivatives of ethylenediamine was revealed against the S. aureus (MRSA) strain, which is resistant to the reference antibiotic ciprofloxacin. Using various test systems, a comparative assessment of the antioxidant activity (AOA) of the synthesized copper complexes and the ligands was carried out. The salen-type complex 4, which has the highest AOA in the model of initiated oxidation of a substrate containing animal lipids, was superior to other copper complexes in the ability to protect erythrocytes under conditions of H₂O₂-induced hemolysis.

The synthesis of new chiral copper(ii) complexes with terpene derivatives of ethylenediamine and the results of studying their antibacterial, antifungal and antioxidant activity in vitro are discussed.     

Antibacterial activity and mechanism of action of a thiophenyl substituted pyrimidine derivative

The issue of multidrug resistant bacteria is a worldwide health threat. To develop new antibacterial agents with new mechanisms of action is thus an urgent request to address this antibiotic resistance crisis. In the present study, a new thiophenyl-pyrimidine derivative was prepared and utilized as an effective antibacterial agent against Gram-positive strains. In the tests against MRSA and VREs, the compound showed higher antibacterial potency than that of vancomycin and methicillin. The mode of action is probably attributed to the effective inhibition of FtsZ polymerization, GTPase activity, and bacterial cell division, which cause bactericidal effects. The compound could be a potential candidate for further development as an effective antibiotic to combat drug-resistant bacteria.

F20 exhibits strong antibacterial activity through interacting with FtsZ.     

Nano-engineering safer-by-design nanoparticle based moth-eye mimetic bactericidal and cytocompatible polymer surfaces

Nanotechnology provides a new design paradigm for alternative antibacterial strategies in the fight against drug-resistant bacteria. In this paper, the enhanced bactericidal action of moth-eye nanocomposite surfaces with a collaborative nanoparticle functional and topography structural mode of action is reported. The moth-eye nanocomposite surfaces are fabricated in combined processing steps of nanoparticle coating and surface nanoimprinting enabling the production of safer-by-design nanoparticle based antibacterial materials whereby the nanoparticle load is minimized whilst bactericidal efficiency is improved. The broad antibacterial activity of the nanocomposite moth-eye topographies is demonstrated against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli and Pseudomonas aeruginosa as model bacteria. The antibacterial performance of the moth-eye nanocomposite topographies is notably improved over that of the neat moth-eye surfaces with bacteria inhibition efficiencies up to 90%. Concurrently, the moth-eye nanocomposite topographies show a non-cytotoxic behaviour allowing for the normal attachment and proliferation of human keratinocytes.

Moth-eye nanocomposite surfaces are fabricated in combined processing steps of nanoparticle coating and surface nanoimprinting enabling the production of safer-by-design antibacterial nanoparticle-based materials.     

Antibacterial effect of 3-p-trans-coumaroyl-2-hydroxyquinic acid,a phenolic compound from needles of Cedrus deodara,on cellular functions of Staphylococcus aureus

A natural phenolic compound, 3-p-trans-coumaroyl-2-hydroxyquinic acid (CHQA) from needles of Cedrus deodara, has been reported to exhibit strong antibacterial activity. In this study, the molecular structural requirements of CHQA for the antibacterial activity and its effect on the cellular functions of Staphylococcus aureus were investigated. The structure–activity relationship analysis revealed that the p-coumaric acid moiety of CHQA was critical for the antibacterial activity, while the esterification between p-coumaric acid and 2-hydroxyquinic acid was unfavorable. Studies of the cellular metabolism demonstrated that CHQA induced a significant decrease in the intracellular ATP concentration but no proportional increase in the extracellular ATP. It was also found that CHQA slightly increased the respiratory activity and succinate dehydrogenase activity of S. aureus. Meanwhile, CHQA decreased the DNA synthesis of S. aureus and directly interacted with DNA through the groove binding mode.

Structure–activity relationship of 3-p-trans-coumaroyl-2-hydroxyquinic acid, a phenolic compound from needles of Cedrus deodara, against Staphylococcus aureus and its effect on the cellular functions.     

Total synthesis of landomycins Q and R and related core structures for exploration of the cytotoxicity and antibacterial properties

Herein, we report the total synthesis of landomycins Q and R as well as the aglycone core, namely anhydrolandomycinone and a related core analogue. The synthesis features an acetate-assisted arylation method for construction of the hindered B-ring in the core component and a one-pot aromatization–deiodination–denbenzylation procedure to streamline the global functional and protecting group manuipulation. Subsequent cytotoxicity and antibacterial studies revealed that the landomycin R is a potential antibacterial agent against methicillin-resistant Staphylococcus aureus.

Herein, we report the total synthesis of landomycins Q and R as well as the aglycone core, namely anhydrolandomycinone and a related core analogue.     

An NIF-doped ZIF-8 hybrid membrane for continuous antimicrobial treatment

Sodium alginate (ALG) composites with ZIF-8 and niflumic acid (NIF) were prepared by a one-pot method at room temperature and characterized by FTIR, SEM and XRD studies. In the composite, ZIF-8 was used as a highly connected node in a supercrosslinked polymer network. In addition, the material exhibits good antibacterial activity against Staphylococcus aureus and Escherichia coli in vitro. Compared to the original ALG membrane and ZIF-8, the ZIF–NIF–ALG membrane has the following advantages: stronger antibacterial properties; slow release of Zn(ii); high drug loading; and longer sustained release time. This research introduces new concepts for the design and manufacture of various antimicrobial membranes and broadens the range of applications of MOFs.

A ZIF-8 hybrid film has shows continuous medical effects, with including antibacterial and anti-inflammatory effects.     

Bioactive silver phosphate/polyindole nanocomposites

Materials capable of releasing reactive oxygen species (ROS) can display antibacterial and anticancer activity, and may also have anti-oxidant capacity if they suppress intracellular ROS (e.g. nitric oxide, NO) resulting in anti-inflammatory activity. Herein we report silver phosphate (Ag₃PO₄)/polyindole (Pln) nanocomposites which display antibacterial, anticancer and anti-inflammatory activity, and have therefore potential for a variety of biomedical applications.

Materials capable of releasing reactive oxygen species (ROS) can display antibacterial and anticancer activity, and may also have antioxidant capacity if they suppress intracellular ROS (e.g. nitric oxide, NO) resulting in anti-inflammatory activity.     

Antimicrobial peptide-modified silver nanoparticles for enhancing the antibacterial efficacy

Antibiotic-resistant bacteria are becoming a serious threat to public health worldwide. To address this problem, we have developed multifunctional peptide (MFP)-coated silver nanoparticles (MFP@AgNPs) for antibacterial studies. MFPs, which can physically adsorb to AgNPs via electrostatic interactions are comprised of a matrix metalloproteinase (MMP) cleavable sequence (PVGLIG), an antimicrobial peptide (tachyplesin-1), and a target peptide (PGP-PEG). The resulting MFP@AgNPs were characterized by various technologies, including UV-vis spectrophotometry, zeta potential analyzer, circular dichroism (CD) spectroscopy, attenuated total reflection-Fourier-transform infrared spectroscopy (ATR-FTIR), and transmission electron microscopy (TEM). The MIC and MBC were investigated against both Gram-positive bacteria and Gram-negative bacteria. The antibacterial activity in vivo was evaluated on MDR-AB (multidrug-resistant Acinetobacter baumannii) infected mice. We found that MFP@AgNPs exhibited antibacterial activity against both Gram-positive bacteria and Gram-negative bacteria. Compared to bare AgNPs, MFP@AgNPs-1 killed MDR-AB faster and more efficiently. SEM images showed that MFP@AgNPs-1 induced cell disruption via cell membrane damage. In vivo studies further confirmed the enhanced antibacterial activity against MDR-AB infections. The developed MFP@AgNPs-1 reduced the cytotoxicity of AgNPs and enhanced the antibacterial activity against MDR-AB in vitro and in vivo, providing a possible solution against multidrug-resistant bacterial infections.

Multifunctional peptides (MFP)-coated silver nanoparticles (MFP@AgNPs) enhanced the antibacterial activity of AgNPs against multidrug-resistant A. baumannii (MDB-AB) strains.     

Enhanced insect-resistance,UV protection,and antibacterial and antistatic properties exhibited by wool fabric treated with polyphenols extracted from mango seed kernel and feijoa peel

The synthetic dyes, antimicrobial and insect-resistant agents, UV radiation absorbents, and antistatic agents that are used to introduce multifunctional properties to textiles are not only toxic to the environment but also require multi-step treatments to achieve them. Toxic antimicrobials are responsible for the growth of drug-resistant bacteria. Nature-derived polyphenols, such as tannin, could be a viable green alternative. In this work, wool fabrics were treated with a commercial tannic acid (PP-1), and also with gallotannin-rich polyphenols extracted from feijoa fruit peel (PP-2) and mango seed kernel (PP-3) to introduce multifunctional properties, i.e. to make the fabric antistatic, insect-resistant, hydrophilic, and able to absorb harmful UV radiation. The effect of the treatment on the colour, colour intensity, surface resistivity, UV radiation absorption, antibacterial activity, and insect-repellence was systematically evaluated. It was found that PP-3-treated fabric exhibited excellent surface hydrophilicity, antibacterial activity against Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa, and insect-resistant activity against the larvae of Tineola bisselliella. PP-3 treatment also provided comparable UV protection and antioxidant activity but was marginally inferior to the UV protection and antioxidant activity exhibited by the PP-1-treated fabric. The commercial tannic acid treated fabric provided the best antistatic properties but the lowest surface hydrophilicity. The developed treatment could provide a green and sustainable alternative to hazardous UV absorbing, antibacterial and insect-resistant agents used in the textile industry.

Wool fabrics were treated with mango kernel and feijoa peel derived polyphenols, which considerably enhanced the antibacterial, insect resistant, antioxidant, UV radiation protection, and antistatic properties of the fabric.     

Synthesis of novel antibacterial and antifungal quinoxaline derivatives

A series of quinoxaline derivatives were designed, synthesized and evaluated as antimicrobial agents against plant pathogenic bacteria and fungi. Some of these compounds exhibited significant antibacterial and antifungal activities in vitro. Compound 5k displayed good antibacterial activity against Acidovorax citrulli (Ac). Compounds 5j and 5t exhibited the most potent anti-RS (Rhizoctonia solani) activity, with the corresponding EC₅₀ values of 8.54 and 12.01 μg mL⁻¹, respectively, which are superior to that of the commercial azoxystrobin (26.17 μg mL⁻¹). Further, the scanning electron microscopy results proved that compound 5j had certain effects on the cell morphology of RS. Moreover, an in vivo bioassay also demonstrated that the anti-RS activity of compound 5j could effectively control rice sheath blight. These results indicate that quinoxaline derivatives could be promising agricultural bactericides and fungicides.

Structure of some commercial agents.     

The oxazolomycin family: a review of current knowledge

Oxazolomycin A and neooxazolomycin were firstly isolated in 1985 by the group of Uemura et al. from the Streptomyces sp. bacteria. To date, there have been reported 15 different natural compounds commonly classified as part of the oxazolomycin family. All oxazolomycin compounds possess extraordinary structures and they represent a synthetic challenge. Such molecules are additionally known for their wide range of biological activity including antibacterial, antiviral and cytotoxic effects. The present review summarizes the structural elucidation and classification of oxazolomycin compounds, their biosynthesis and biological activity. It is further focused on the total syntheses of oxazolomycins and one formal synthesis reported to date.

Oxazolomycin A and neooxazolomycin were firstly isolated in 1985 by the group of Uemura et al. from the Streptomyces sp. bacteria.     

Design,synthesis and biological evaluation of N-arylsulfonyl carbazoles as novel anticancer agents

In this work, a set of structurally diverse synthetic carbazoles was screened for their anticancer activities. According to structure–activity relationship studies, carbazoles with an N-substituted sulfonyl group exhibited better anticancer activity. Moreover, compound 8h was discovered to show the most potent anticancer effects on Capan-2 cells by inducing apoptosis and cell cycle arrest in G2/M phase. Finally, the in vivo study demonstrated that 8h prevented the tumor growth in PANC-1 and Capan-2 xenograft models without apparent toxicity.

In this work, a set of structurally diverse synthetic carbazoles was screened for their anticancer activities.     

Synthesis of C-prenylated analogues of stilbenoid methyl ethers and their cyclic dihydrobenzopyranyl derivatives as potential anti-inflammatory agents

An efficient and versatile synthesis of the naturally occurring C-prenylated stilbenoid methyl ethers and their synthetic analogues is presented. The synthesis represents a six step convergent process including an optimised C-prenylation method. Furthermore, during the demethylation process, six new dihydro-benzopyranyl derivatives were obtained and isolated.

An efficient and versatile synthesis of the naturally occurring C-prenylated stilbenoid methyl ethers and synthetic analogs has been developed.     

Enhanced anti-Escherichia coli properties of Fe-doping in MgO nanoparticles

Hetero-elements doping is an effective way to modify the composition and nanostructure of metal oxides. These modifications could lead to changes in physical and chemical properties correspondingly. In this study, Fe-doped MgO nanoparticles (NPs) were synthesized by simple calcination method in air. The antibacterial activity of MgO NPs against Escherichia coli (E. coli, ATCC 25922) was significantly improved as shown by the bactericidal efficacy test results. According to X-ray diffraction (XRD) results, Fe was successfully doped into MgO lattice and mainly adopted interstitial doping. The Fe-doping led to increased oxygen vacancies and O_A content (from 13.5% to 41.3%) on MgO surface, which may have facilitated the reactive oxygen species (ROS) generation and bacteria death. The wrinkled and sunken E. coli surface after contact with Fe-doped MgO NPs also confirmed the existence of adsorption damage mechanism. Thus, the antibacterial activity enhancement against E. coli was originated from the synergistic effect of increased ROS concentration and the interaction with Fe-doped MgO NPs.

Fe was successfully incorporated into MgO nanoparticles (NPs), which has significant enhanced the antibacterial property of MgO NPs against E. coli.