Catalytic asymmetric carbenoid α-C-H insertion of ether.

Significant advancements have been made in catalytic asymmetric α-C-H bond functionalization of ethers via carbenoid insertion over the past decade. Effective asymmetric catalytic systems, featuring a range of chiral metal catalysts, have been established for the enantioselective synthesis of diverse ether substrates. This has led to the generation of various enantioenriched, highly functionalized oxygen-containing structural motifs, facilitating their application in the asymmetric synthesis of bioactive natural products.

Divergent synthesis of bis(indolyl)methanes via FeIII-catalysed regioselective dehydrogenative coupling reactions: a biomimetic approach to 6,6'-bis-(debromo)-gelliusine F.

The divergent dehydrogenative coupling reactions of tryptamines with the catalysis of nontoxic FeIII salts in the presence of DDQ as the co-oxidant have been developed. Remarkably, the transformations feature a rapid and regioselective assembly of diverse 2,8'- and N1,8'-bis(indolyl) methane derivatives from readily-available starting materials by simply changing the FeIII salt and reaction temperature. Besides, the fast reaction rate, mild reaction conditions, low catalyst cost and easy operations make this methodology quite useful. The synthetic utility was further demonstrated in the biomimetic synthesis of 6,6'-bis-(debromo)-gelliusine F.

Development of Strigolactones as Novel Autophagy/Mitophagy Inhibitors against Colorectal Cancer Cells by Blocking the Autophagosome-Lysosome Fusion.

Inhibition of autophagy has been widely viewed as a promising strategy for anticancer therapy. However, few effective and specific autophagy inhibitors have been reported. Herein, we described the design, synthesis, and biological characteristics of new analogues of strigolactones (SLs), an emerging class of plant hormones, against colorectal cancers. Among them, an enantiopure analogue 6 exerted potent and selective cytotoxicity against colorectal cancer cells, but not normal human colon mucosal epithelial cells, which were further confirmed by the plate colony formation assay. Moreover, it significantly inhibited tumor growth in an HCT116 xenograft mouse model with low toxicity. Mechanistically, it is associated with selective induction of cell apoptosis and cell cycle arrest. Remarkably, 6 acted as a potent autophagy/mitophagy inhibitor by selectively increasing the autophagic flux while blocking the autophagosome-lysosome fusion in HCT116 cells. This study features stereo-defined SLs as novel autophagy inhibitors with high cancer cell specificity, which paves a new path for anticolorectal cancer therapy.

Acid-promoted intra- and intermolecular [2+2] cycloaddition of indoles to aryl alkynes to access cyclobutene-fused indolines.

Herein, we have reported the first example of both intra- and intermolecular [2+2] cycloaddition of the electron-rich indoles and unactivated aryl alkynes promoted by the combination of Fe(NO3)3 and HNO3, which highlights efficient and selective access to several different types of functionalized cyclobutene-fused indolines from readily available starting materials with cheap catalysts and simple operations.

Effects of fenugreek seed extracts on growth performance and intestinal health of broilers.

The purpose of this experiment was to study the effects of fenugreek seed extract (FSE) on the growth performance, intestinal morphology, intestinal immunity and cecal micro-organisms in yellow-feathered broilers. A total of 240 one-day-old male yellow-feathered broilers were selected and randomly assigned to four treatments with 6 replicates per group and ten broilers per replicate. Started from the third day, birds were fed with basal diet (CON group) or basal diet supplemented with 30 mg/kg Zinc bacitracin (ZB group), or basal diet supplemented with 50 (D-FSE group) or 100 (H-FSE group) mg/kg FSE, respectively. The experiment lasted for 56 d. The results showed that dietary FSE supplementation improved average daily weight gain (ADG) and ratio of feed to weight gain (F: G) (P < 0.01), increased intestinal villus height (VH), villus height to crypt depth ratio (V/C) (P < 0.05), serum concentrations of IL-10, and the contents of secretory immunoglobulin A (sIgA) (P < 0.05), as well as decreased the activity of iNOS (P < 0.05). The high-throughput sequencing results showed that dietary FSE supplementation increased the alpha diversity of cecal microbes, and Firmicutes, Bacteroidetes, Verrucomicrobia and Proteobacteria taken up 95% of all phyla detected, FSE significantly reduced Campylobacter, Synergistes, and Lachnoclostridium abundance (P ≤ 0.05). There were significant difference in more than 30 KEGG pathways between FSE added group and control group or ZB group. FSE supplementation, in other words, maintained gut microbiota homeostasis while improving broiler growth performance. As a result, FSE has the potential to replace prophylactic antibiotic use in poultry production system.

Oral administration of octacosanol modulates the gut bacteria and protects the intestinal barrier in ulcerative colitis mice.

Octacosanol (Oct), a kind of long-chain fatty alcohol extracted from rice bran was applied to study its effects on alleviating ulcerative colitis (UC). Oct was orally administered at 10 mg/kg (Oct-L) and 30 mg/kg (Oct-H) to dextran sulfate sodium (DSS)-induced mice. Here, we reported that oral administration of 30 mg/kg Oct can significantly prevent the weight loss, colon shortening, and decrease the disease activity index (DAI) score. Oct-H supplementation modified the intestinal flora by lowering the Firmicutes/Bacteroidetes (F/B) ratio, increasing the abundance of Prevotellaceae, S24-7, Turicibacter, and meanwhile decreasing Enterococcus and Stenotrophomonas. Based on the PICRUSt2 analysis, Oct-H may exert effects by anti-inflammation and xenobiotics degradation. Furthermore, short-chain fatty acids (SCFAs) levels were raised and the integrity of the gut barrier was protected. In conclusion, Oct-H can relieve clinical symptoms, modulate the gut bacteria and protect the intestinal barrier in UC mice, suggesting the potential of Oct as a food supplementation in alleviating UC. PRACTICAL APPLICATIONS: Ulcerative colitis (UC) is a hard-to-cure disease, with increasing morbidity in recent years. Therefore, finding out a food supplement to alleviate UC is very meaningful. In this work, we showed that octacosanol significantly alleviated ulcerative colitis in mice. We revealed, for the first time, octacosanol's effects on protecting the integrity of the gut barrier, modulating the intestinal flora and its metabolism (SCFAs). Therefore, octacosanol was expected to prevent colitis in an all-round way. Our research might also lay the theoretical foundation for the further development of related functional foods.

Major royal jelly proteins alleviate non-alcoholic fatty liver disease in mice model by regulating disordered metabolic pathways.

Nonalcoholic fatty liver disease (NAFLD), the major cause of global chronic hepatic injury, has obtained increasing attention while the current drug treatment still laid safety hazards. Major royal jelly proteins (MRJPs), the water-soluble proteins enriched in royal jelly (RJ), were applied to study its effects on improving NAFLD in the NAFLD mouse model. Herein, we demonstrated that intaking of 250-500 mg/kg/day MRJPs significantly decreased the rate of obesity, dyslipidemia, hepatic steatosis, and insulin resistance. Next, TOF to MRM ("TM") widely targeted metabolomics (untargeted metabolomics + widely targeted metabolomics) was further used to explore the potential mechanism, and we found that 500 mg/kg MRJPs alleviated lipid metabolism, oxidative stress, and inflammation mainly by regulating the metabolisms of alpha-linolenic acid, linoleic acid, arachidonic acid, and biosynthesis of unsaturated fatty acids. Moreover, by detecting multiple oxidative stress factors and inflammatory cytokines, we found that MRJPs indeed exerted antioxidant and anti-inflammatory effects. Together, we demonstrated that MRJPs could mediate the progress of NAFLD through the "multi-component-multi-target-multi-pathway" mechanism, which could be considered as an ideal functional food in alleviating NAFLD. PRACTICAL APPLICATIONS: Royal jelly (RJ) is a bee product with high nutritional value. Major royal jelly proteins (MRJPs) are water-soluble proteins in RJ. Our research showed that MRJPs significantly ameliorated NAFLD induced by a high-fat diet in mice, suggesting that MRJPs could be used as an active ingredient to help improve NAFLD, which was beneficial for the development of related functional foods and the economic value of RJ. Moreover, the metabolic pathways involved in the ameliorative effect of MRJPs were investigated, which provided new ideas for the prevention and treatment of NAFLD.

Chrysin Improves Glucose and Lipid Metabolism Disorders by Regulating the AMPK/PI3K/AKT Signaling Pathway in Insulin-Resistant HepG2 Cells and HFD/STZ-Induced C57BL/6J Mice.

Natural products with minor side effects have been reported to be an effective adjuvant therapy for glucose and lipid metabolism disorders. Chrysin, a flavone, has a wide range of physiological effects, such as antioxidant, anti-inflammatory, anti-diabetes, anti-hyperlipidemia, and hepatoprotective. This study was designed to explore the effects and mechanism of chrysin on metabolic syndrome using insulin-resistant HepG2 cells and HFD/STZ-induced C57BL/6J mice. The results indicated that chrysin significantly decreased insulin resistance, oxidative stress, inflammation, and liver injury. In addition, chrysin improved glycogen synthesis and fatty acid oxidation and inhibited gluconeogenesis and fatty acid synthesis by regulating GSK3ß, G6Paes, PEPCK, SREBP1, FAS, and ACC1. Furthermore, the results of western blot and real-time PCR experiments demonstrated that chrysin modulated glucose and lipid metabolism through the AMPK/PI3K/AKT signaling pathway. Treatment with the AMPK inhibitor verified that AMPK activation is positively correlated with chrysin activity on glycolipid metabolism. This study confirms that chrysin is a potential treatment for glucose and lipid metabolism disorders.

Carnosic acid alleviates depression-like behaviors on chronic mild stressed mice via PPAR-γ-dependent regulation of ADPN/FGF9 pathway.

RATIONALE: The pathway of adiponectin (ADPN)/fibroblast growth factor 9 (FGF9) was recently thought as a key role in the development of depression. ADPN is crucially regulated by peroxisome proliferator-activated receptor-gamma (PPAR-γ). Natural material carnosic acid (CA) has been applied for therapeutics of mental disorders. OBJECTIVES: To evaluate the antidepressive effect of CA in stress-treated mice and define whether its effects is involved in the regulation of ADPN/FGF9 pathway. METHODS: In vivo study, the levels of ADPN and FGF9 in both serum and hippocampus tissues, the expressions of ADPN receptor 2 (AdipoR2) in hippocampus and PPAR-γ in abdominal adipose, as well as the pathological changes of hippocampus were determined in 28-day period of chronic unpredictable mild stress (CUMS)-induced depression model of male ICR (Institute of Cancer Research) mice or adipo-/- mice. In vitro study, the level of ADPN and the mRNA expressions of both ADPN and PPAR-γ were determined in mouse 3T3-L1 preadipocytes. RESULTS: In vivo study, treatment with CA (50 or 100 mg/kg per day) for 21 days markedly suppressed depressive-like behaviors, the elevating levels of FGF9 and decreasing levels of ADPN in both serum and hippocampus tissues, the downregulating protein and mRNA expressions of AdipoR2 in hippocampus and PPAR-γ in abdominal adipose, as well as the pathological injury of hippocampus induced by CUMS in male ICR mice. The antidepressive effects of CA were markedly attenuated in male CUMS-treated adipo-/- mice. In vitro study, incubation with CA (3-30 µmol/L) for 24 h could concentration-dependently upregulate the mRNA expressions of both PPAR-γ and ADPN as well as increase the level of ADPN. The experiments using PPAR-γ-specific inhibitor GW9662 and transient transfection with mutated PPAR-γ-binding site promotor constructs showed that the activation of PPAR-γ mediated CA-induced ADPN expression in adipocytes. CONCLUSIONS: CA could significantly improve stress-induced depressive disorder, which may be related to regulating the dysfunction of ADPN-FGF9 pathway via activating PPAR-γ in adipocytes.

Total synthesis of natural products using photocycloaddition reactions of arenes.

The photocycloaddition reaction of benzene with alkenes has become a significant approach for organic chemists and thus has been frequently utilized as a key step in the total synthesis of natural products. In this mini-review, the recent developments in [4 + 2] and [2 + 2] photocycloaddition reactions will be emphasized in constructing core scaffolds of complex natural products. By combining them together, we aim to demonstrate the utility and reinstate the importance of this methodology.

Cold-pressed Canola Oil Reduces Hepatic Steatosis by Modulating Oxidative Stress and Lipid Metabolism in KM Mice Compared with Refined Bleached Deodorized Canola Oil.

The quality of canola oil is affected by different extraction methods. The effect of cold-pressed canola oil (CPCO) diet and traditional refined bleached deodorized canola oil (RBDCO) diet on lipid accumulation and hepatic steatosis in mice were investigated. The body weight, peroxisome proliferator-activated receptor-α concentration, serum lipid profile, insulin sensitivity, and oxidative stress were increased in mice fed with CPCO diet, which had higher unsaturated fatty acid, tocopherols, phytosterols, and phospholipids but lower saturated fatty acid than RBDCO, after 12 weeks,. Moreover, CPCO significantly increased tocopherols and phytosterols content in liver and reduced liver cholesterol contents and lipid vacuoles accumulation than RBDCO. Also, serum proinflammatory cytokines, 3-hydroxy-3-methylglutary coenzyme A reductase expression level, lipogenic enzymes, and transcriptional factors such as sterol regulatory element-binding proteins 1c, acetyl-CoA carboxylase, and fatty acid synthase in the liver were also markedly downregulated from CPCO diet mice. Overall, CPCO can reduce lipid accumulation and hepatic steatosis by regulating oxidative stress and lipid metabolism in Kun Ming mice compared with RBDCO. PRACTICAL APPLICATION: The results suggested that more bioactive components were contained in cold-pressed canola oil (CPCO) rather than refined bleached deodorized canola oil (RBDCO). CPCO could lower the risk of obesity and hyperlipidemia, reduce lipid accumulation, and prevent hepatic steatosis. It could be considered as a kind of better edible oil than RBDCO.

Vitexin compound 1, a novel extraction from a Chinese herb, suppresses melanoma cell growth through DNA damage by increasing ROS levels.

BACKGROUND: Vitex negundo L (Verbenaceae) is an aromatic shrub that is abundant in Asian countries. A series of compounds from Vitex negundo have been used in traditional Chinese medicine for the treatment of various diseases. Cutaneous melanoma is one of the most aggressive malignancies. A significant feature of melanoma is its resistance to traditional chemotherapy and radiotherapy; therefore, there is an urgent need to develop novel treatments for melanoma. METHODS: We first examined the effects of VB1 (vitexin compound 1) on cell viability by CCK-8 (cell counting kit) and Colony Formation Assay; And then, we analyzed the apoptosis and cell cycle by flow cytometry, verified apoptosis by Immunoblotting. The in vivo effect of VB1 was evaluated in xenograft mouse model. Potential mechanisms of VB1's antitumor effects were explored by RNA sequencing and the key differential expression genes were validated by real-time quantitative PCR. Finally, the intracellular reactive oxygen species (ROS) level was detected by flow cytometry, and the DNA damage was revealed by Immunofluorescence and Immunoblotting. RESULTS: In this study, we show that VB1, which is a compound purified from the seed of the Chinese herb Vitex negundo, blocks melanoma cells growth in vitro and in vivo, arrests the cell cycle in G2/M phase and induces apoptosis in melanoma cell lines, whereas the effects are not significantly observed in normal cells. To study the details of VB1, we analyzed the alteration of gene expression profiles after treatment with VB1 in melanoma cells. The findings showed that VB1 can affect various pathways, including p53, apoptosis and the cell cycle pathway, in a variety of melanoma cell lines. Furthermore, we confirmed that VB1 restored the P53 pathway protein level, and then we demonstrated that VB1 significantly induced the accumulation of ROS, which resulted in DNA damage in melanoma cell lines. Interestingly, our results showed that VB1 also increased the ROS levels in BRAFi (BRAF inhibitor)-resistant melanoma cells, leading to DNA cytotoxicity, which caused G2/M phase arrest and apoptosis. CONCLUSIONS: Taken together, our findings indicate that vitexin compound 1 might be a promising therapeutic Chinese medicine for melanoma treatment regardless of BRAFi resistance.

The chemical diversity and structure-based evolution of non-peptide CXCR4 antagonists with diverse therapeutic potential.

The CXC chemokine receptor 4 (CXCR4) is a highly reserved G-protein coupled 7-transmembrane (TM) chemokine receptor which consists of 352 amino acids. CXCR4 has only one endogenous chemokine ligand of CXCL12, besides several other natural nonchemokine ligands such as extracellular ubiquitin and noncognate ligand of MIF. CXCR4 strongly binds to CXCL12 and the resulting CXCLl2/CXCR4 axis is the molecular basis of their various biological functions, which include: (1) mediating immune and inflammatory response; (2) regulation of hematopoietic stem cell migration and homing; (3) an essential co-receptor for HIV entry into host cells; (4) participation in the process of embryonic development; (5) malignant tumor invasion and metastasis; (6) myocardial infarction, ischemic stroke and acute kidney injury. Correspondingly, CXCR4 antagonists find potential therapeutic applications in HIV infection, as well as hematopoietic stem cell migration, inflammation, immune-related diseases, tumor and ischemic diseases. Recently, great achievements have been made and a number of non-peptide CXCR4 antagonists with diversity scaffolds have been discovered. In this review, the discovery of small molecule CXCR4 antagonists focused on the structures, activities, evolution and development of representative CXCR4 antagonists is comprehensively described. The central role of CXCR4 in diverse cellular signaling pathways and its involvement in several diseases progressions are discussed as well.

[Genome-wide analysis and functional prediction of the Trihelix transcription factor family in rice].

The Trihelix transcription factor family plays an essential role in plant growth, development and stress response. However, the studies about identification and analysis of this gene family in rice on the genome-wide level have not been reported. In this study, 31 members of the Trihelix family, which contain highly conserved and characteristic trihelix domain through sequence clustering and functional domains analysis, were identified in rice genome database using bioinformatic tools. These members could be classified into 5 subfamilies (I~V) based on the evolutionary relationship and domain characteristics. Clustering analyses of the Trihelix family in rice, Arabidopsis, Brachypodium distachyom and Sorghum bicolor showed that each species contained different members of subfamily although the classification of the Trihelix family were consistent in these four species, which indicated that the differentiation of the Trihelix gene family occur earlier than that of these species. The conserved motifs in the Trihelix family of rice analyzed using the MEME program were highly consistent with the results of clustering analyses. Intraspecific and interspecific chromosomal replication in partial Trihelix family members were found to exist in rice and between rice and other species through chromosome replication analysis. Microarray data analysis revealed diverse expression patterns of Trihelix family genes in different tissues of rice or in response to six different phytohormones. Moreover, 20 members of the Trihelix transcription factor family were found to interact with other proteins in rice using RiceFRIEND online database analysis. Therefore, our results preliminarily identified the evolution, chromosome distribution and replication, expression patterns, phytohormones response of the Trihelix transcription factor family and the interaction between trihelix family proteins and other proteins in rice, which will provide a basis to further reveal the molecular evolution and biological function of the Trihelix transcription factor family.

Hexadentate 3-hydroxypyridin-4-ones with high iron(III) affinity: design, synthesis and inhibition on methicillin resistant Staphylococcus aureus and Pseudomonas strains.

A range of hexadentate 3-hydroxypyridin-4-ones have been synthesized. These compounds were found to possess a high affinity for iron(III), with logK1 values of about 34 and pFe values over 30. Antimicrobial assays indicated that they can inhibit the growth of three clinical isolates of methicillin resistant Staphylococcus aureus (MRSA) and three clinical isolates of Pseudomonas, suggesting that hexadentate 3-hydroxypyridin-4-ones have potential application in the treatment of wound infections.

Novel hypovirulence-associated RNA mycovirus in the plant-pathogenic fungus Botrytis cinerea: molecular and biological characterization.

Botrytis cinerea is a pathogenic fungus causing gray mold on numerous economically important crops and ornamental plants. This study was conducted to characterize the biological and molecular features of a novel RNA mycovirus, Botrytis cinerea RNA virus 1 (BcRV1), in the hypovirulent strain BerBc-1 of B. cinerea. The genome of BcRV1 is 8,952 bp long with two putative overlapped open reading frames (ORFs), ORF1 and ORF2, coding for a hypothetical polypeptide (P1) and RNA-dependent RNA polymerase (RdRp), respectively. A -1 frameshifting region (designated the KNOT element) containing a shifty heptamer, a heptanucleotide spacer, and an H-type pseudoknot was predicted in the junction region of ORF1 and ORF2. The -1 frameshifting role of the KNOT element was experimentally confirmed through determination of the production of the fusion protein red fluorescent protein (RFP)-green fluorescent protein (GFP) by the plasmid containing the construct dsRed-KNOT-eGFP in Escherichia coli. BcRV1 belongs to a taxonomically unassigned double-stranded RNA (dsRNA) mycovirus group. It is closely related to grapevine-associated totivirus 2 and Sclerotinia sclerotiorum nonsegmented virus L. BcRV1 in strain BerBc-1 was found capable of being transmitted vertically through macroconidia and horizontally to other B. cinerea strains through hyphal contact. The presence of BcRV1 was found to be positively correlated with hypovirulence in B. cinerea, with the attenuation effects of BcRV1 on mycelial growth and pathogenicity being greatly affected by the accumulation level of BcRV1.

[Role of ERK/FoxO3a signal axis in inhibitory effect of vitexin 1 (VB-1) in HepG2 cell proliferation].

OBJECTIVE: To investigate whether the ERK/FoxO3a signal axis could induce the inhibitory effect of vitexin 1 (VB-1) in HepG2 cell proliferation. METHOD: The MTT method was adopted to observe the effect of different concentrations of VB-1 on human hepatoma carcinoma cell line HepG2 and immortalized human embryo liver cell line L-02. The cell growth was assessed by the clone formation assay. The protein phosphorylation levels of ERK1/2 and FoxO3a were measured by the western blot. RESULT: VB-1 inhibited the viability of HepG2 cell line in a concentration-dependent manner, with a weak effect on L-02 cell line. VB-1 could effectively inhibit the anchorage-dependent growth of HepG2 cells, and reduce the expression levels of pERK1/2 and pFoxO3a in a concentration-dependent manner. MEK1/2 inhibitor PD98059 could enhance VB-1' s effect in inhibiting HepG2 cell proliferation and ERK1/2, FoxO3a phosphorylation. CONCLUSION: VB-1 inhibits the proliferative activity of hepatoma carcinoma cell line HepG2 by blocking the ERK/FoxO3a signal axis.

Protective effect of vitexin compound B-1 against hypoxia/reoxygenation-induced injury in differentiated PC12 cells via NADPH oxidase inhibition.

Vitexin compound B-1 (VB-1) is a novel member of the vitexins family isolated from the seeds of the Chinese herb Vitex negundo. This study aims to investigate whether VB-1 is able to protect nerve cells against oxidative injury and whether the antioxidative effects of VB-1 occur through a mechanism involving the inhibition of NADPH oxidase (NOX) in a manner of hypoxia-inducible factor 1α (HIF-1α)-dependent. To establish a neuronal in vitro model of oxidative stress, the differentiated PC12 cells were subjected to 5 h of hypoxia followed by 20 h of reoxygenation (H/R). Three dosages of VB-1 (10(-8), 10(-7), and 10(-6) M) were chosen to evaluate the effect of VB-1 on H/R-induced injury and the underlying mechanisms. At the end of the experiments, culture mediums and cells were collected for analysis of cellular apoptosis, lactate dehydrogenase (LDH) and caspase 3/7-like activities, reactive oxygen species (ROS) levels, 4-hydroxynonenal (4-HNE) and malondialdehye (MDA) contents, and HIF-1α and NOX expression, respectively. Our results showed that cell injury (indicated by apoptosis ratio, caspase 3/7-like activity, and LDH release), oxidative stress (indicated by ROS production, 4-HNE, and MDA contents), NOX activity, and NOX expression (NOX2 and NOX4 isoforms) were dramatically increased in PC12 cells following H/R, which were attenuated in the presence of VB-1 at dosage of 10(-7) or 10(-6) M. There was no significant change in HIF-1α expression in all experimental groups. These results provide evidence that VB-1 is able to protect the PC12 cells against H/R-induced injury through a mechanism involving the suppression of NOX expression and subsequent reduction of ROS production. The effect of VB-1 on H/R-induced NOX expression is independent on HIF-1α inhibition.

Design, synthesis, and antimicrobial evaluation of hexadentate hydroxypyridinones with high iron(III) affinity.

A range of hexadentate 3-hydroxypyridin-4-ones (HPOs) with high affinity for iron(III) has been synthesized. The log stability constants of two HPO-iron complexes (logK1 ) were determined to be over 34, and pFe values of the two HPOs were determined to be over 31. Antimicrobial assay indicated that they are able to markedly inhibit the growth of both Gram-positive and Gram-negative bacteria. Compounds 14a and 14e were found to exhibit the strongest inhibitory activity against Staphyloccocus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli, with MIC values of 8, 8, 16, and 8 µg/mL, respectively. These results indicate that hexadentate 3-hydroxypyridin-4-ones have potential application as antimicrobial agents, especially in the treatment of wound infection.

In vitro antimicrobial activity of hydroxypyridinone hexadentate-based dendrimeric chelators alone and in combination with norfloxacin.

The antimicrobial activity of one 3-hydroxypyridin-4-one (HPO) hexadentate (1) and three HPO hexadentate-based dendrimeric chelators (2-4) was evaluated. They were found to exhibit marked inhibitory effect on the growth of two Gram-positive bacteria and two Gram-negative bacteria. The combination treatment of dendrimeric chelator 2 with norfloxacin against Staphyloccocus aureus and Escherichia coli showed a dramatic synergistic bactericidal effect. As the dendrimeric chelator has a large molecular weight, its combination with norfloxacin may find application in the treatment of external infections.