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The isolation and characterization of bioactive metabolites from Streptomyces species continue to represent a vital area of research, given their potential in natural product drug discovery. In this study, we characterize a new siderophore called legonoxamine I, together with a known compound, streptimidone, from the talented soil bacterium Streptomyces sp. MA37, using chromatographic techniques and spectroscopic analysis. Legonoxamine I is a new holo-siderophore, which is likely to be a derailed product from the biosynthetic pathway of legonoxamine A. We also demonstrate that legonoxamine A possesses potent anticancer activity (IC50 = 2.2 µM), exhibiting a remarkable ~30-fold increase in potency against MCF-7 ATCC HTB-22 breast cancer cells compared to desferrioxamine B, a structural analogue of legonoxamine A (IC50 = 61.1 µM). Comparing the structural difference between legonoxamine A and desferrioxamine B, it is deduced that the phenylacetyl moiety in legonoxamine A may have contributed significantly to its enhanced potency. Our findings contribute to the growing library of Streptomyces-derived metabolites and underscore the genus' potential as a promising source of lead compounds. [ABSTRACT FROM AUTHOR]

This mini‐review focuses on recent developments in hydroxamate‐based metal–organic frameworks (MOFs), which exhibit unique structures and properties distinct from those of carboxylate‐based MOFs. Hydroxamates (RCONHO−) form MOFs with novel structural motifs and functionalities. In this review, synthetic strategies, structural characteristics, and functional applications of key examples of hydroxamate‐based MOFs are described, providing insights into the influence of the hydroxamate ligand on the MOF properties compared to that of the carboxylate‐based analogues. [ABSTRACT FROM AUTHOR]

Pathogenic bacteria must secure the uptake of nutritional metals such as iron for their growth, making their import systems attractive targets for the development of new antimicrobial modalities. In the pathogenic bacterium Streptococcus pyogenes, the iron uptake system FtsABCD transports iron encapsulated by siderophores of the hydroxamate class. However, the inability of S. pyogenes to produce these metabolites makes the biological and clinical relevance of this route unresolved. Herein, we demonstrated that the periplasmic binding protein FtsB recognizes not only the hydroxamate siderophore ferrichrome, as previously documented, but also ferrioxamine E (FOE), ferrioxamine B (FOB), and bisucaberin (BIS), each of them with high affinity (nM level). Up to seven aromatic residues in the binding pocket accommodate the variable backbones of the different siderophores through CH-π interactions, explaining ligand promiscuity. Collectively, our observations revealed how S. pyogenes exploits the diverse xenosiderophores produced by other microorganisms as iron sources to secure this precious nutrient. [Display omitted] • FtsB shows promiscuity toward different hydroxamates in complex with various metals • Key binding regions within FtsB were identified by structural and mutagenesis analysis • An aromatic "glove" accommodating siderophores of different size explains promiscuity • The binding mechanism of FtsB seems to be conserved across bacterial species Siderophores are small molecules that microorganisms use to harvest iron from their environment. Fernández-Pérez et al. report the promiscuous binding of the hydroxamate siderophore transporter FtsB from Streptococcus pyogenes. FtsB enables the bacterium to use different types of xenosiderophores hydroxamates with a mechanism that is broadly conserved in other bacteria. [ABSTRACT FROM AUTHOR]

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To qualify as competent sorbents for airborne contaminants such as iodine vapor, permanent porosity and chemical stability are key criteria for the selection of candidate metal-organic frameworks (MOFs). To ensure these characteristics, in the present study, an unsymmetrical bifunctional ligand incorporating both carboxylic acid and hydroxamic acid groups was employed for MOF [Zn(CBHA)](DMF) [SUM-13; CPHA = 4-carboxyphenylhydroxamate, DMF = N,N-dimethylformamide] design and synthesis. Though coupled with Zn2+, which does not typically yield kinetically robust MOFs with hard acids, the SUM-13 featuring differentiated coordination modes of chelating, bridging and monodentate bonding exhibited exceptional chemical stability and permanent porosity, with a Brunauer–Emmett–Teller (BET) surface area of 296.9 m2/g and a total pore volume of 0.1196 cm3/g. Additionally, with porosity and open metal sites at the five-coordinate Zn2+ centers, SUM-13 was demonstrated to be an eligible iodine adsorbent, reaching a maximum uptake of 796 mg/g. These findings underscore the validity and potential of the design strategy in constructing stable metal–organic frameworks. [ABSTRACT FROM AUTHOR]

Microorganisms produce siderophores, which are low-molecular-weight iron chelators when iron availability is limited. The present analyzed the role of LNPF1 as multifarious PGPR for improving growth parameters and nutrient content in peanut and soil nutrients. Such multifarious PGPR strains can be used as effective bioinoculants for peanut farming. In this work, rhizosphere bacteria from Zea mays and Arachis hypogaea plants in the Salem area of Tamil Nadu, India, were isolated and tested for biochemical attributes and characteristics that stimulate plant growth, such as the production of hydrogen cyanide, ammonia (6 µg/mL), indole acetic acid (76.35 µg/mL), and solubilizing phosphate (520 µg/mL). The 16S rRNA gene sequences identified the isolate LNPF1 as Pseudomonas fluorescens with a similarity percentage of 99% with Pseudomonas sp. Isolate LNPF1 was evaluated for the production of siderophore. Siderophore-rich supernatant using a Sep Pack C18 column and Amberlite-400 Resin Column (λmax 264) produced 298 mg/L and 50 mg/L of siderophore, respectively. The characterization of purified siderophore by TLC, HPLC, FTIR, and 2D-NMR analysis identified the compound as desferrioxamine, a hydroxamate siderophore. A pot culture experiment determined the potential of LNPF1 to improve iron and oil content and photosynthetic pigments in Arachis hypogaea L. and improve soil nutrient content. Inoculation of A. hypogea seeds with LNPF1 improved plant growth parameters such as leaf length (60%), shoot length (22%), root length (54.68%), fresh weight (47.28%), dry weight (37%), and number of nuts (66.66) compared to the control (untreated seeds). This inoculation also improved leaf iron content (43.42), short iron content (38.38%), seed iron (46.72%), seed oil (31.68%), carotenoid (64.40%), and total chlorophyll content (98.%) compared to control (untreated seeds). Bacterized seeds showed a substantial increase in nodulation (61.65%) and weight of individual nodules (95.97) vis-à-vis control. The results of the present study indicated that P. fluorescens might be utilized as a potential bioinoculant to improve growth, iron content, oil content, number of nuts and nodules of Arachishypogaea L., and enrich soil nutrients. [ABSTRACT FROM AUTHOR]

In an attempt to search for natural product-derived antifungal agents, a series of novel anethole-derived hydroxamate compounds were designed and synthesized. Their chemical structures were characterized by 1H NMR, 13C NMR, FT-IR, ESI-MS, and element analysis. It was found from the in vitro antifungal activity bioassay that some of the target compounds showed better antifungal activity than that of the commercial fungicide thifluzamide. For example, compounds 6p (R= m -NO 2), 6q (R= p -NO 2), 6o (R= o -NO 2), and 6 t (R= p -Cl- o -F) displayed inhibitory rates of 88.2%, 88.2%, 80.9% and 80.9% against Gibberella zeae , respectively, which were better than that of the commercial fungicide thifluzamide. Meanwhile, compounds 6p (R= m -NO 2) and 6r (R= o , o -Cl) exhibited certain broad-spectrum inhibitory activity. Besides, the 3D-quantitative structure-activity relationship (3D-QSAR) study was carried out to investigate the relationship between the molecular structures of the target compounds and their antifungal activity. The possible binding mode between the target compound and succinate dehydrogenase (SDH) was also explored by molecular docking. [Display omitted] • Twenty anethole-derived hydroxamate compounds were designed and synthesized. • Some target compounds exhibited good antifungal activity. • The 3D-QSAR model was established to reveal the structure-activity relationship. • The binding mode of the target compound with SDH was explored by molecular docking. [ABSTRACT FROM AUTHOR]

Ongoing therapy for human parasite infections has a few known drugs but with serious side effects and the problem of drug resistance, impelling us to discover novel drug candidates with newer mechanisms of action. Universally, this has boosted the research in the design and development of novel medicinal agents as antiparasitic drugs with a novel mode of action. Histone deacetylase inhibitors (HDACis) are used in a vast variety of diseases due to their anti-inflammatory properties. Drug repurposing strategies have already approved HDACis as cancer therapeutics and are now under investigation for many parasitic infections. Along with the expression of the gene, histone deacetylase (HDAC) enzymes also act as a slice of great multi-subunit complexes, targeting many non-histones, changing systemic and cellular levels signaling, and producing different cell-based specified effects. Zinc (Zn2+)- and nicotinamide adenine dinucleotide (NAD+)-dependent HDACs of parasites play pivotal roles in the alteration of gene expression of parasites. Some of them are already known to be responsible for the survival of several parasites under odd circumstances; thus, targeting them for therapeutic interventions will be novel for potential antiparasitic targets. This point of view outlines the knowledge of both class-I and class-II HDACis and sirtuin inhibitors that emerged to be the key players in the treatment of human parasitic disorders like Leishmaniasis, Schistosomiasis, Malaria, Trypanosomiasis, and Toxoplasmosis. This review also focuses on repurposing opportunities and challenges in HDAC inhibitors that are preceded by their clinical development as potent new antiparasitic drugs.

Abstract Recent events involving iron ore tailings dam collapses have emphasized the need for developing alternative ways of depositing tailings. This study aims to evaluate the effects of using three hydroxamates and a sulfosuccinamate as collectors in the direct flotation of iron ore tailings, using a bench flotation. The best result obtained on bench flotation was tested in a pneumatic cell. The sample used in this study (10.8% of Fe) consists of quartz and hematite. The Aero® 6494 Promoter hydroxamate showed the highest selectivity among the analyzed reagents, reaching 64.31% of Fe in the final product of the test with the < 150 µm sample. The possibility of using these reagents as constituents of a mixed collector with dodecylamine was also investigated. In this case, the Aero® 845 Promoter sulfosuccinamate yielded the best results, with 62.84% of Fe and 59.01% of metallurgical recovery of Fe. The synergistic effect between the two reagents might be explained by the stability of the monolayer formed by the intercalation of the ions from the dodecylamine and the Aero® 845 Promoter, which reduces the electrostatic repulsion between ions of the same species This mixed collector was tested in a pneumatic cell. However, it had a lower performance in terms of Fe metallurgical recovery than in a bench-scale cell test, mainly for the finest particles, due to the greater control of the process’s variables in the bench cell.

Ongoing therapy for human parasite infections has a few known drugs but with serious side effects and the problem of drug resistance, impelling us to discover novel drug candidates with newer mechanisms of action. Universally, this has boosted the research in the design and development of novel medicinal agents as antiparasitic drugs with a novel mode of action. Histone deacetylase inhibitors (HDACis) are used in a vast variety of diseases due to their anti-inflammatory properties. Drug repurposing strategies have already approved HDACis as cancer therapeutics and are now under investigation for many parasitic infections. Along with the expression of the gene, histone deacetylase (HDAC) enzymes also act as a slice of great multi-subunit complexes, targeting many non-histones, changing systemic and cellular levels signaling, and producing different cell-based specified effects. Zinc (Zn2+)- and nicotinamide adenine dinucleotide (NAD+)-dependent HDACs of parasites play pivotal roles in the alteration of gene expression of parasites. Some of them are already known to be responsible for the survival of several parasites under odd circumstances; thus, targeting them for therapeutic interventions will be novel for potential antiparasitic targets. This point of view outlines the knowledge of both class-I and class-II HDACis and sirtuin inhibitors that emerged to be the key players in the treatment of human parasitic disorders like Leishmaniasis, Schistosomiasis, Malaria, Trypanosomiasis, and Toxoplasmosis. This review also focuses on repurposing opportunities and challenges in HDAC inhibitors that are preceded by their clinical development as potent new antiparasitic drugs. [ABSTRACT FROM AUTHOR]

Siderophores are iron-chelating agents produced by almost all microorganisms in response to iron deficiency. Due to the requirement of iron for cell growth and metabolism, siderophore-mediated acquisition of iron plays a central role in determining the ability of different microorganisms to colonize plant roots and contributes to microbial interactions in the plant rhizosphere. In this study, five new Pseudomonas (Q14B, Q13B, Q7B, Q6B, Q1B), isolated from the rhizosphere of tomato in Morocco, were examined for siderophores production capacity. The results show that all five isolates produced siderophores on both solid and liquid mediums. In liquid medium, the highest level of production is obtained by Q13B (53.8%). Concerning siderophores’ chemical types, the five strains of Pseudomonas produce two types of siderophores hydroxamate and catecholate. It was shown by the peaks of absorbance in the wavelength 495 and between 420-450 nm for catecholate and hydroxamate-type siderophores respectively. The results showed that the production of siderophores is progressively inhibited with increasing concentrations of iron in the medium. The maximum production was obtained with a concentration of 0.5 μM, while the lowest was recorded at 10.0 μM of iron. The results of this study showed that the five Pseudomonas isolates producing siderophores could be potential biological control agents. [ABSTRACT FROM AUTHOR]

Recent events involving iron ore tailings dam collapses have emphasized the need for developing alternative ways of depositing tailings. This study aims to evaluate the effects of using three hydroxamates and a sulfosuccinamate as collectors in the direct flotation of iron ore tailings, using a bench flotation. The best result obtained on bench flotation was tested in a pneumatic cell. The sample used in this study (10.8% of Fe) consists of quartz and hematite. The Aero® 6494 Promoter hydroxamate showed the highest selectivity among the analyzed reagents, reaching 64.31% of Fe in the final product of the test with the < 150 µm sample. The possibility of using these reagents as constituents of a mixed collector with dodecylamine was also investigated. In this case, the Aero® 845 Promoter sulfosuccinamate yielded the best results, with 62.84% of Fe and 59.01% of metallurgical recovery of Fe. The synergistic effect between the two reagents might be explained by the stability of the monolayer formed by the intercalation of the ions from the dodecylamine and the Aero® 845 Promoter, which reduces the electrostatic repulsion between ions of the same species This mixed collector was tested in a pneumatic cell. However, it had a lower performance in terms of Fe metallurgical recovery than in a bench-scale cell test, mainly for the finest particles, due to the greater control of the process’s variables in the bench cell. [ABSTRACT FROM AUTHOR]

The current research has been conceptualized to see the impact of Trichoderma harzianum synthesized siderophore in alleviation of heavy metal stress [lead (Pb), mercury (Hg) and cadmium (Cd)] first time for Solanum melongena under high concentration. Alongside, we reported impact of siderophore in form of product for S. melongena seed germination in presence of heavy metal stress under high and low concentration. Optimization of siderophore production was achieved using Response Surface Methodology (RSM) that resulted in an increment of siderophore production. Through RSM, 92.7% siderophore unit was obtained whereas without using RSM only 89.1% siderophore unit was obtained. The novelty of this work lies in the fact that T. harzianum synthesized metal chelators have not been used previously for S. melongena seed germination under different heavy metal stress (Pb, Hg and Cd). Based on obtained results, we have found that in case of siderophore treated seeds, germination percentage was increased such as in 400 mg/kg of Cd and Pb concentration (with siderophore) seeds germination % was 66.6 ± 3.4% and 62.5 ± 6.8% respectively, whereas non-siderophore treated seeds germination % was 30.5 ± 5.1% and 27.7 ± 5.1% respectively. In presence of 100 mg/kg of Hg with siderophore, seed germination % was 59.7 ± 7.8% whereas in Hg stressed seeds (non siderophore treated) germination was 19.2 ± 3.9% respectively. The cluster heat map was deployed to analyze the effect of siderophore treatment on S. melongena seedling under heavy metal stress. Obtained results suggested that we can deploy the use of RSM to enhance the siderophore production using different factors such as carbon, nitrogen, pH and FeCl3 etc. It is worthwhile approach to use siderophore as plant growth promotor in heavy metal stress due to its metal chelating activity. [ABSTRACT FROM AUTHOR]

Our study focuses on hydroxamate-type siderophores from Pseudomonas putida BP25, known for chelating ferric iron and aiding microbial growth in iron-deficient environments. Confirmed through CAS-agar and tetrazolium tests, a purified siderophore extract was obtained via ion-exchange chromatography. Applying varying concentrations of this siderophore to rice seedlings demonstrated concentration-dependent effects on shoot and root phenotypes. Prophylactic application on rice leaves significantly reduced blast severity (68.7%–97.0%), surpassing curative application (47.5%–86.87%). Additionally, the siderophore treatment elevated peroxidase, polyphenol oxidase, and total phenols in rice plants. Defense-related genes linked to salicylic acid (OsPR1.1, OsNPR1 , and OsPDF2.2), and other pathways (Oshox24, OsCLE , and OsGLP3-3, OsEIN2.4 , and OsCSE) promoting blast suppression showed upregulation. However, the OsACS6 gene associated with ethylene-induced internodal elongation was significantly downregulated. Overall, our findings propose that the siderophore from P. putida BP25 induces defense gene transcription, offering potential for sustainable rice production via bio-formulation. [ABSTRACT FROM AUTHOR]

The flotation enrichment of fine-particle wolframite played a crucial role in production of strategic key metal tungsten. In this paper, N-[(3-hydroxyamino)-propoxy]-N-hexyl dithiocarbamate (HAHD) was designed to strengthen the flotation recovery of wolframite. The in situ AFM images clearly exhibited that the pre-activation of wolframite with Pb2+ ions significantly enhanced the self-assemble and aggregation of HAHD on its surface, and its surface hydrophobicity and floatability dramatically improved. The FTIR and XPS results recommended a chemisorption of HAHD to the Pb(II)-activated wolframite, and in the surface HAHD-Pb(II) complexes, both dithiocarbamate and hydroxamate groups chelated Pb(II) to deliver the four-membered and five-membered ring configurations. The double-site adsorption rendered a closed loop anchor of HAHD on the Pb(II)-activated wolframite surface, which essentially weakened the hydration of OH- ions toward Pb2+, Fe2+ or Mn2+ ions in/on wolframite interface. In addition, the hexyl group exhibits a strong hydrophobization, and the dithiocarbamate displays a selective affinity against alkaline earth metal minerals. These encouraged HAHD to be a strong-power and selective collector for wolframite versus calcite at its low dose. N-[(3-hydroxyamino)-propoxy]-N-hexyl dithiocarbamate promotes wolframite flotation. In situ AFM showed the self-assemble of HAHD on Pb(II)-activated wolframite surface. Both dithiocarbamate and hydroxamate reacted with the Pb(II)-activated wolframite. The double-site adsorption rendered a closed loop anchor to weaken surface hydration. HAHD is a strong-power collector for selective flotation of wolframite against calcite. [ABSTRACT FROM AUTHOR]

The survival of living organisms depends on iron, one of the most abundant metals in the Earth's crust. Nevertheless, this micronutrient is poorly available in our aerobic atmosphere as well as inside the mammalian host. This problem is circumvented by the expression of high affinity iron uptake machineries, including the production of siderophores, in pathogenic fungi. Here we demonstrated that F. pedrosoi , the causative agent of the neglected tropical disease chromoblastomycosis, presents gene clusters for siderophore production. In addition, ten putative siderophore transporters were identified. Those genes are upregulated under iron starvation, a condition that induces the secretion of hydroxamates, as revealed by chrome azurol S assays. RP-HPLC and mass spectrometry analysis allowed the identification of ferricrocin as an intra- and extracellular siderophore. F. pedrosoi can grow in different iron sources, including the bacterial ferrioxamine B and the host proteins ferritin, hemoglobin and holotransferrin. Of note, addition of hemoglobin, lactoferrin and holotransferrin to the growth medium of macrophages infected with F. pedrosoi enhanced significantly fungal survival. The ability to produce siderophores in iron limited conditions added to the versatility to utilize different sources of iron are strategies that certainly may contribute to fungal survival inside the host. [ABSTRACT FROM AUTHOR]

Targeting metalloproteinases has been in the focus of drug design for a long time. However, meprin α and β emerged as potential drug targets just recently and are linked to several diseases with different pathological background. Nevertheless, the validation of meprins as suitable drug targets still requires highly potent and selective inhibitors as chemical probes to elucidate their role in pathophysiology. Albeit highly selective inhibitors of meprin β have already been reported, only inhibitors of meprin α with modest activity or selectivity are known. Starting from recently reported heteroaromatic scaffolds, the aim of this study was the optimisation of meprin α and/or meprin β inhibition while keeping the favourable off-target inhibition profile over other metalloproteases. We report potent pan-meprin inhibitors as well as highly active inhibitors of meprin α with superior selectivity over meprin β. The latter are suitable to serve as chemical probes and enable further target validation. [ABSTRACT FROM AUTHOR]

Monitoring the microenvironment within specific cellular regions is crucial for a comprehensive understanding of life events. Fluorescent probes working in different ranges of pH regions have been developed for the local imaging of different pH environments. Especially, rhodamine-based fluorescent pH probes have been of great interest due to their ON/OFF fluorescence depending on the spirolactam ring's opening/closure. By introducing the N-alkyl-hydroxamic acid instead of the alkyl amines in the spirolactam of rhodamine, we were able to tune the pH range where the ring opening and closing of the spirolactam occurs. This six-membered cyclic hydroxamate spirolactam ring of rhodamine B proved to be highly fluorescent in acidic pH environments. In addition, we could monitor pH changes of lysosomes in live cells and zebrafish. [ABSTRACT FROM AUTHOR]

The mining industry aims to promote responsible chemical use during mineral processing operations to minimize the chemical contamination. Hydroxamic acids, which can form strong chelates with metals, have been shown to have less health and environmental issues when compared to xanthate collectors. In this work, the performance of benzohydroxamic acid (BHA) as a collector for galena, chalcopyrite, and quartz was evaluated. The minerals were conditioned with different concentrations (1.5, 3, and 4.5 kg/t) of collector at pHs 8, 9, and 10. The result showed that the treatment of the mineral surfaces with BHA enhanced the flotation recoveries of the sulfide minerals. High concentrations of benzohydroxamate anion, the protonic dissociation product of BHA, existed at basic pHs, where a chemical reaction between the anion and a metal cation on the mineral surface resulted in the adsorption of the collector onto the mineral surface. The microflotation results showed that the BHA collector was able to successfully recover galena and chalcopyrite. Their flotation recovery was dependent on the conditioning pH. Galena showed a high flotation recovery (up to 86%) at both pH 9 and 10, whereas chalcopyrite became most hydrophobic at pH values of 8 and 9 (up to 88%). None of the BHA concentrations or conditioning pHs was able to enhance quartz recovery beyond 7%. The research results have implications in the application of BHA for the froth flotation of galena and chalcopyrite. [ABSTRACT FROM AUTHOR]

We report a new hydroxamate‐based yttrium MOF, named MOF‐419 [Y(HCOO)(BDH)], with rod‐SBUs. The compound was synthesized employing chelating construction of benzene‐1,4‐hydroxamate (BDH2−) linkers, and the use of formic acid as the modulator was found to be crucial for the formation of rod‐shaped SBUs. MOF‐419 shows permanent porosity and has a BET surface area of 1130 m2/g. Its hydrophobic pore environment and gas sorption properties were demonstrated through the combination of single crystal X‐ray diffraction and nitrogen, carbon dioxide, and water sorption experiments. We envision that these results will aid the study and understanding of rod MOFs with chelating linkages. [ABSTRACT FROM AUTHOR]

Iron is a micronutrient required by almost all living organisms. Despite being essential, the availability of this metal is low in aerobic environments. Additionally, mammalian hosts evolved strategies to restrict iron from invading microorganisms. In this scenario, the survival of pathogenic fungi depends on high-affinity iron uptake mechanisms. Here, we show that the production of siderophores and the reductive iron acquisition system (RIA) are employed by Cladophialophora carrionii under iron restriction. This black fungus is one of the causative agents of chromoblastomycosis, a neglected subcutaneous tropical disease. Siderophore biosynthesis genes are arranged in clusters and, interestingly, two RIA systems are present in the genome. Orthologs of putative siderophore transporters were identified as well. Iron starvation regulates the expression of genes related to both siderophore production and RIA systems, as well as of two transcription factors that regulate iron homeostasis in fungi. A chrome azurol S assay demonstrated the secretion of hydroxamate-type siderophores, which were further identified via RP-HPLC and mass spectrometry as ferricrocin. An analysis of cell extracts also revealed ferricrocin as an intracellular siderophore. The presence of active high-affinity iron acquisition systems may surely contribute to fungal survival during infection. [ABSTRACT FROM AUTHOR]

HDAC6 is predominantly found in the cytoplasm and is mainly responsible for deacetylation of non-histone proteins including α-tubulin in microtubules, the HSP90 chaperone, cortactin, etc. Inhibition of HDAC6 has been shown to be efficacious in treating cancer, neurodegenerative diseases, heart failure, pain, fibrosis, and inflammatory diseases. This review focuses on the recent more drug-like selective HDAC6 inhibitors, especially the two major chemotypes of mercaptoacetamides and fluoroalkyl-oxadiazoles. The latter class lacks structural alert thus has low potential for toxicities. As a consequence, fluoroalkyl-oxadiazoles, especially difluoromethyl 1,3,4-oxadiazoles, are promising HDAC6 inhibitors for the treatment of chronic diseases such as heart failure, neurodegenerative diseases, fibrosis, and pain. [ABSTRACT FROM AUTHOR]

The NIS synthetase family of enzymes responsible for the biosynthesis of siderophores is increasingly associated with bacterial virulence. Proteins in this class represent outstanding potential drug targets, assuming that basic biochemical and structural characterizations can be completed. Towards this goal, we have mated an improved synthesis of the non-commercial amino acid N-hydroxy-N-succinylcadaverine (HSC, 6) with an isothermal titration calorimetry (ITC) assay that profiles the iterative stages of HSC trimerization and macrocyclization by NIS synthetase DesD from Streptomyces coelicolor. HSC synthesis begins with multigram-scale Gabrielle and tert-butyl N-(benzyloxy)carbamate alkylations of 1-bromo-5-chloropentane following prior literature, but the end-game reported herein has two advantages for greater material throughput: (1) hydrogenolysis of benzyl ether and Cbz blocking groups is best accomplished with Pearlman's catalyst at 40 psi of H2 and (2) purification of neutral (zwitterionic) HSC is effected by simple flash chromatography over silica gel in MeOH. HSC is subsequently shown to be a substrate for NIS synthetase DesD, which catalyzes three successive amide bond syntheses via adenyl monophosphate ester intermediates. We quantify and present the iterative and overall enzyme kinetic constants associated with formation of the cyclotrimeric siderophore desferrioxamine E (dfoE, 1). [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of Tetrahydro-β-carboline-based hydroxamate derivatives as HDAC inhibitors were designed and synthesized. • Compound 11g showed potent HDAC1 inhibition. • Compound 11g effectively inhibited colony formation of A549 cells. • Compound 11g significantly inhibited the proliferation and promoted cycle arrest as well as apoptosis of A549 cells. • Compound 11g enhanced ROS generation and DNA damage accumulation to induce apoptosis in A549 cells. Histone deacetylases (HDACs) are validated drug targets for various therapeutic applications. A series of Tetrahydro-β-carboline-based hydroxamate derivatives, designed as HDAC inhibitors (HDACis), were synthesized. Compound 11g exhibited strong inhibitory activity against HDAC1 and the A549 cancer cell line. Additionally, this compound increased the levels of acetylated histone H3 and H4. Notably, 11g effectively arrested A549 cells in the G2/M phase and also increased ROS production and DNA damage, thereby inducing apoptosis. Further molecular docking experiments illustrated the potential interactions between compound 11g and HDAC1. These findings suggested that the novel Tetrahydro-β-carboline-based HDACis could serve as a promising framework for further optimization as anticancer agents. [ABSTRACT FROM AUTHOR]

The emergence of resistant bacteria takes place, endangering the effectiveness of antibiotics. A reason for antibiotic resistance is the presence of lactamases that catalyze the hydrolysis of β-lactam antibiotics. An inhibitor of serine-β-lactamases such as clavulanic acid binds to the active site of the enzymes, thus solving the resistance problem. A pressing issue, however, is that the reaction mechanism of metallo-β-lactamases (MBLs) hydrolyzing β-lactam antibiotics differs from that of serine-β-lactamases due to the existence of zinc ions in the active site of MBLs. Thus, the development of potential inhibitors for MBLs remains urgent. Here, the ability to inhibit MBL from Bacillus anthracis (Bla2) was investigated in silico and in vitro using compounds possessing two hydroxamate functional groups such as 3-chloro-N-hydroxy-4-(7-(hydroxyamino)-7-oxoheptyl)benzamide (Compound 4) and N-hydroxy-4-(7-(hydroxyamino)-7-oxoheptyl)-3-methoxybenzamide (Compound 6). In silico docking and molecular dynamics simulations revealed that both Compounds 4 and 6 were coordinated with zinc ions in the active site, suggesting that the hydroxamate group attached to the aromatic ring of the compound plays a crucial role in the coordination to the zinc ions. In vitro kinetic analysis demonstrated that the mode of inhibitions for Compounds 4 and 6 were a competitive inhibition with Ki values of 6.4 ± 1.7 and 4.7 ± 1.4 kcal/mol, respectively. The agreement between in silico and in vitro investigations indicates that compounds containing dihyroxamate moieties may offer a new avenue to overcome antibiotic resistance to bacteria. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is an urgent as well as huge medical challenge, which is associated with poor prognosis and responsiveness to chemotherapies. Since epigenetic changes are highly implicated in TNBC tumorigenesis and development, inhibitors of histone deacetylases (HDACIs) could represent a promising therapeutic strategy. Although clinical trials involving single HDACIs showed disappointing results against TNBC, recent studies emphasize the high potential impact of HDACIs in controlling TNBC. In addition, encouraging results stem from new compounds designed to obtain isoform selectivity and/or polypharmacological HDAC approach. The present review provides a discussion of the HDACIs pharmacophoric models and of the structural modifications, leading to compounds with a potent activity against TNBC progression. [ABSTRACT FROM AUTHOR]

Two new oxidovanadium(V) complexes, [VOL1L] (1) and [VOL2L]·CH3OH (2·CH3OH), where L1 and L2 are the dianionic form of N’-(3-bromo-2-hydroxybenzylidene)picolinohydrazide (H2L1) and 2-chloro-N’-(2-hydroxy-3-methoxybenzylidene)benzohydrazide (H2L2), respectively, and L is the monoanionic form of 2-hydroxybenzohydroxamic acid (HL), were prepared and characterized by elemental analysis, infrared and electronic spectroscopy. Structures of the complexes were further confirmed by single crystal X-ray determination. The V atoms in the complexes are in octahedral coordination. The hydrazone ligands coordinate to the V atoms through the phenolate O, imino N, and enolate O atoms. The hydroxamate ligand coordinates to the V atom through the carbonyl and hydroxy O atoms. The complexes show effective antibacterial activity against B. subtilis, S. aureus and E. coli. The presence of Cl substitute group in the complex may enhance the antibacterial activity.

Froth flotation of fine minerals has always been an important research direction in terms of theory and practice. In this paper, the effect and mechanism of Fe3+ on improving surface hydrophobicity and flotation of fine monazite using sodium octyl hydroxamate (SOH) as a collector were investigated through a series of laboratory tests and detection measurements including microflotation, fluorescence spectrum, zeta potential, and X-ray photoelectron spectroscopy (XPS). Flotation tests have shown that fine monazite particles (−26 + 15 μm) cannot be floated well with the SOH collector compared to the coarse fraction (−74 + 38 μm). However, adding a small amount of Fe3+ to the pulp before SOH can significantly improve the flotation of fine monazite. This is because the addition of Fe3+ promotes the adsorption of SOH and greatly improves the hydrophobicity of the monazite surface. This can result in the formation of a more uniform and dense hydrophobic adsorption layer, as shown by the fluorescence spectrum and zeta potential results. From the XPS results, Fe3+ reacts with surface O atoms on the surface of monazite to form a monazite–Osurf–Fe group that acts as a new additional active site for SOH adsorption. A schematic model was also proposed to explain the mechanism of Fe3+ for improving surface hydrophobicity and flotation of fine monazite using octyl hydroxamate as a collector. The innovative point of this study is using a simple reagent scheme to float fine mineral particles rather than traditional complex processes.

Belinostat là thuốc có khả năng ức chế enzyme HDAC khá tốt, được sử dụng điều trị các khối u ác tính về huyết học và khối u rắn. Trong nghiên cứu này, các dẫn xuất tương tự belinostat đã được tổng hợp thành công qua quy trình đơn giản và hiệu quả, phù hợp với quy mô phòng thí nghiệm tại Việt Nam. Quy trình trải qua 6 bước: i) Tạo m-nitrobenzaldehyde sử dụng tác nhân KNO3/H2SO4; ii) Phản ứng Wittig sử dụng chất thân hạch ylide; iii) Khử nhóm –NO2 thành –NH2; iv) Phản ứng tạo sulfonyl; v) Phản ứng thế thân hạch với các amine; và vi) Phản ứng tạo thành hydroxamate với tác nhân NH2OH. Kết quả các dẫn xuất đã được tổng hợp thành công với hiệu suất toàn phần tương đối cao, cấu trúc được xác định dựa trên các phương pháp phổ nghiệm bao gồm 1H-NMR và MS và đánh giá khả năng ức chế HDAC bằng phương pháp in silico.

Both thioether and hydroxamate groups are excellent iron ligands. Herein, to improve the properties of hydroxamic acid and the recovery of tungsten-minerals, a surfactant containing thioether and hydroxamate groups, 2-(benzylthio)-acetohydroxamic acid (BTHA), was introduced to separate wolframite from fluorite. The properties, predicted by Density Functional Theory (DFT) calculations and Molecular Dynamics (MD), indicated that BTHA, as a multifunctional surfactant (i.e., thioether and hydroxamate groups), could enhance its hydrophobicity and selectively adsorb on the desired mineral surfaces. The experimental results of micro-flotation and contact angles confirmed BTHA had a strong collecting ability and good selectivity toward wolframite versus fluorite. The adsorption mechanism, surveyed through zeta potential, solution chemical analysis and XPS, demonstrated only electrostatic adsorption on fluorite surfaces, while chemisorption and hydrogen bonding would be produced on wolframite surfaces. The thioether and hydroxamate groups could co-absorb onto wolframite's surfaces to form Fe S bonds and five-membered hydroxamate-(O, O)-Fe rings. Unlabelled Image • 2-(benzylthio)-acetohydroxamic acid (BTHA) was first used as wolframite collectors. • The flotation performances were predicted by molecular simulation. • BTHA exhibited superior affinity to wolframite against fluorite. • BTHA's thioether and hydroxamate groups co-anchored on wolframite. [ABSTRACT FROM AUTHOR]

A novel nanocaptor (GO-HDX) was designed based on the graphene oxide nanosheets functionalized with hydroxamate moieties that enabled the selective removal and recovery of extremely radioactive uranyl ions from wastewater samples. The synthesized nanocaptor (GO-HDX) was well-characterized using elemental analysis, FT-IR and Raman spectroscopy, and X-ray diffraction (XRD). The U(VI) removal from aqueous solution with GO-HDX was investigated in terms of essential factors (initial pH, contact time and temperature), adsorption isotherm and thermodynamics were examined. The UO22+ ions adsorption under the studied conditions was well-fitted to the Freundlich model as well as to the pseudo-first-order model. [ABSTRACT FROM AUTHOR]

Polyhydroxamate desferrioxamines (DFO) are nontoxic siderophores endowed with high potential for development of therapeutic chelating agents. Herein, we report a modular and convergent strategy for diverse synthesis of macrocyclic and linear DFOs. The strategy employed orthogonally protected N‐hydroxy‐N‐succinylcadaverine building blocks, which allowed bidirectional extension of the DFO structure. The efficiency of the new strategy was demonstrated by the total synthesis of 44‐membered macrocyclic DFO‐T1, as well as four related DFO compounds in 11–13 linear steps and 2.1 %–10 % overall yields. Comparison of the iron binding affinity of the DFOs revealed DFO‐E as the best chelator. [ABSTRACT FROM AUTHOR]

[Display omitted] We previously studied 2-aryl-2-(3-indolyl)acetohydroxamates as potential agents against melanoma. These compounds were ineffective in a mouse melanoma xenograft model, most likely due to unfavorable metabolic properties, specifically due to glucuronidation of the N -hydroxyl of the hydoxamic moiety. In the present work, we prepared a series of analogues, 2-aryl-2-(3-indolyl)acetamides and their oxazoline derivatives, which do not contain the N -hydroxyl group. We investigated the structure–activity relationship in both series of compounds and found that the 2-naphthyl is a preferred group at C-2 of the indole in the amide series, whereas the tetralin moiety is favorable in the same location in the oxazoline series. Overall, three compounds in the amide series have GI 50 values as low as 0.2–0.3 µM and the results clearly indicate that the N -hydroxyl group is not necessary for high potency in vitro. [ABSTRACT FROM AUTHOR]

Fluorescent Pseudomonas (FP) is a major group of plant growth promoting rhizobacteria and a well-known synthesizer of siderophores, which imparts a selective advantage on rhizosphere competence and their biocontrol traits. The present study was aimed at examining the factors affecting the production of siderophores and their potential biocontrol traits. Sixteen FP isolates were shortlisted based on their siderophore-producing ability in chrome azural S medium. The isolates were checked for variations in siderophore production under varying incubation times, temperatures, pH, iron (Fe3+) concentrations and mutagens. In addition, the iron binding affinity of siderophores, mycelial inhibition assay and plant growth promotion traits were assessed. Results showed that the siderophore production was highly influenced by the time of incubation, changes in pH, temperature and iron concentration. Chemical characterization showed that the produced siderophores were hydroxamates. Maximum siderophore production was observed at pH 7 whereas UV and EtBr exposure invariably suppressed siderophore production drastically in all isolates. All FPs from maize rhizosphere showed excellent siderophore production which could be due to the competence in strategy-II of the plant rhizosphere and significant growth inhibition on Fusarium oxysporum. Our results suggest the inclination of siderophores to iron, in terms of various criteria affecting production and the possible role of environmental mutations that affect the natural iron harvesting mechanism.

A set of compounds incorporating carbon-based zinc-binding groups (ZBGs), of the type PhX (X = COOH, CONH2, CONHNH2, CONHOH, CONHOMe), and the corresponding derivatives with sulphur(VI)-based ZBGs (X = SO3H, SO2NH2, SO2NHNH2, SO2NHOH, SO2NHOMe) were tested as inhibitors of all mammalian isoforms of carbonic anhydrase (CA, EC 4.2.1.1), CA I–XV. Three factors connected with the ZBG influenced the efficacy as CA inhibitor (CAI) of the investigated compounds: (i) the pKa of the ZBG; (ii) its geometry (tetrahedral, i.e. sulphur-based, versus trigonal, i.e. carbon-based ZBGs), and (iii) orientation of the organic scaffold induced by the nature of the ZBG. Benzenesulphonamide was the best inhibitor of all isoforms, but other ZBGs led to interesting inhibition profiles, although with an efficacy generally reduced when compared to the sulphonamide. The nature of the ZBG also influenced the CA inhibition mechanism. Most of these derivatives were zinc binders, but some of them (sulfonates, carboxylates) may interact with the enzyme by anchoring to the zinc-coordinated water molecule or by other inhibition mechanisms (occlusion of the active site entrance, out of the active site binding, etc.). Exploring structurally diverse ZBGs may lead to interesting new developments in the field of CAIs.

Iron (Fe) is the fourth most abundant element on earth and represents an essential nutrient for life. As a fundamental mineral element for cell growth and development, iron is available for uptake as ferric ions, which are usually oxidized into complex oxyhydroxide polymers, insoluble under aerobic conditions. In these conditions, the bioavailability of iron is dramatically reduced. As a result, microorganisms face problems of iron acquisition, especially under low concentrations of this element. However, some microbes have evolved mechanisms for obtaining ferric irons from the extracellular medium or environment by forming small molecules often regarded as siderophores. Siderophores are high affinity iron-binding molecules produced by a repertoire of proteins found in the cytoplasm of cyanobacteria, bacteria, fungi, and plants. Common groups of siderophores include hydroxamates, catecholates, carboxylates, and hydroximates. The hydroxamate siderophores are commonly synthesized by fungi. L-ornithine is a biosynthetic precursor of siderophores, which is synthesized from multimodular large enzyme complexes through non-ribosomal peptide synthetases (NRPSs), while siderophore-Fe chelators cell wall mannoproteins (FIT1, FIT2, and FIT3) help the retention of siderophores. S. cerevisiae, for example, can express these proteins in two genetically separate systems (reductive and nonreductive) in the plasma membrane. These proteins can convert Fe (III) into Fe (II) by a ferrous-specific metalloreductase enzyme complex and flavin reductases (FREs). However, regulation of the siderophore through Fur Box protein on the DNA promoter region and its activation or repression depend primarily on the Fe availability in the external medium. Siderophores are essential due to their wide range of applications in biotechnology, medicine, bioremediation of heavy metal polluted environments, biocontrol of plant pathogens, and plant growth enhancement.

Background and purpose: Angiogenesis and lymphangiogenesis are major routes for metastatic spread of tumor cells. It thus represent the rational targets for therapeutic intervention of cancer. Recently, we showed that a novel aliphatic hydroxamate-based compound, WMJ-S-001, exhibits anti-angiogenic, anti-inflammatory and anti-tumor properties. However, whether WMJ-S-001 is capable of suppressing lymphangiogenesis remains unclear. We are thus interested in exploring WMJ-S-001's anti-lymphangiogenic mechanisms in lymphatic endothelial cell (LECs).Experimental approach: WMJ-S-001's effects on LEC proliferation, migration and invasion, as well as signaling molecules activation were analyzed by immunoblotting, flow-cytometry, MTT, BrdU, migration and invasion assays. We performed tube formation assay to examine WMJ-S-001's ex vivo anti-lymphangiogenic effects.Key results: WMJ-S-001 inhibited serum-induced cell proliferation, migration, invasion in murine LECs (SV-LECs). WMJ-S-001 reduced the mRNA and protein levels of survivin. Survivin siRNA significantly suppressed serum-induced SV-LEC invasion. WMJ-S-001 induced p53 phosphorylation and increased its reporter activities. In addition, WMJ-S-001 increased p53 binding to the promoter region of survivin, while Sp1 binding to the region was decreased. WMJ-S-001 induced p38 mitogen-activated protein kinase (p38MAPK) activation. p38MPAK signaling blockade significantly inhibited p53 phosphorylation and restored survivin reduction in WMJ-S-001-stimulated SV-LCEs. Furthermore, WMJ-S-001 induced survivin reduction and inhibited cell proliferation, invasion and tube formation of primary human LECs.Conclusions and Implications: These observations indicate that WMJ-S-001 may suppress lymphatic endothelial remodeling and reduce lymphangiogenesis through p38MAPK-p53-survivin signaling. It also suggests that WMJ-S-001 is a potential lead compound in developing novel agents for the treatment of lymphangiogenesis-associated diseases and cancer.

Single crystals of the title complex, [Zn(C7H5N2O4)2(C2H6OS)2] or [Zn(NBZH)2(DMSO)2], were isolated from a dimethyl sulfoxide (DMSO) solution containing [Zn(NBZH)2]·2H2O (NBZH = 3-nitrobenzohydroxamate anion). The asymmetric unit comprises of one O,O′-chelating NBZH anion, one O-bound DMSO ligand and one zinc(II) cation localized on an inversion centre. The three-dimensional crystal packing includes N—H...O and C—H...O hydrogen bonding, as well as O...H and H...H contacts identified by Hirshfeld isosurface analysis.

One of the most important aspects in any flotation separation is the choice of the flotation collector. For this reason, based on both our recent research developments and the results from other researchers, this detailed review focuses on fundamental surface chemistry features of fatty acid, hydroxamate, phosphonate, and phosphate as collectors for the flotation recovery of the rare earth (RE) mineral, bastnaesite, including selectivity considerations with respect to separation from calcite, barite, and quartz. [ABSTRACT FROM AUTHOR]

• S -[(2-hydroxyamino)-2-oxoethyl]- N , N -dimethyl-dithiocarbamate (HAOMDC) is designed. • The hydroxamate-functionalized tip is firstly exploited by self-assemble of HAOMDC on Au tip. • Adhesion forces of the protonated and deprotonated hydroxamate groups to minerals are compared. • Relationship between adhesion and flotation separation is established. • Octyl hydroxamic acid binds to surface iron atoms of wolframite via Fe-O bonding. Separation process facilitated by selective adsorption of chemical reagents can be modulated through an in-depth understanding of reagent-surface interaction, which is of both fundamental and practical importance in a wide range of industrial applications. Hydroxamate is a class of widely used reagents in chemical and mineral engineering that can selectively adsorb on certain minerals (e.g., malachite, wolframite and rare-earth minerals) to facilitate their separation from polymetallic ores by froth flotation. In this study, the hydroxamate-mineral interaction has been probed at nanoscale using atomic force microscopy (AFM), where the hydroxamate-functionalized tips were fabricated by self-assembly of a novel reagent S -[(2-hydroxyamino)-2-oxoethyl]- N , N -dimethyl-dithiocarbamate (HAOMDC) on Au tips. The adhesion energy between hydroxamate-functionalized tip and wolframite was found much higher than that with calcite and quartz, attributed to the stronger bonding between hydroxamate groups and surface Fe atoms of wolframite. Under alkaline condition, the deprotonated hydroxamate groups, due to stronger electron donating power, exhibited enhanced adhesion on wolframite and calcite as compared to that under acidic condition. X-ray photoelectron spectroscopy (XPS) results showed the adsorption of octyl hydroxamic acid (OHA) on wolframite possibly via the formation of five-membered-ring structure. The AFM force results support the froth flotation data that OHA exhibits superior selectivity for wolframite against calcite and quartz. This work provides a useful approach to evaluate the reagent-solid interaction in selective separation processes, with implications for the development of novel chemical additives in many engineering and environmental applications. [ABSTRACT FROM AUTHOR]

Iron is part of many redox and other enzymes and, thus, it is essential for all living beings. Many oxic environments have extremely low concentrations of free iron. Therefore, many prokaryotic species evolved siderophores, i.e., small organic molecules that complex Fe3+ with very high affinity. Siderophores of bacteria are intensely studied, in contrast to those of archaea. The haloarchaeon Haloferax volcanii contains a gene cluster that putatively encodes siderophore biosynthesis genes, including four iron uptake chelate (iuc) genes. Underscoring this hypothesis, Northern blot analyses revealed that a hexacistronic transcript is generated that is highly induced under iron starvation. A quadruple iuc deletion mutant was generated, which had a growth defect solely at very low concentrations of Fe3+, not Fe2+. Two experimental approaches showed that the wild type produced and exported an Fe3+-specific siderophore under low iron concentrations, in contrast to the iuc deletion mutant. Bioinformatic analyses revealed that haloarchaea obtained the gene cluster by lateral transfer from bacteria and enabled the prediction of enzymatic functions of all six gene products. Notably, a biosynthetic pathway is proposed that starts with aspartic acid, uses several group donors and citrate, and leads to the hydroxamate siderophore Schizokinen.

In this paper, we report on the chemistry of the rare South African Actinomycete Kribbella speibonae strain SK5, a prolific producer of hydroxamate siderophores and their congeners. Two new analogues, dehydroxylated desferrioxamines, speibonoxamine 1 and desoxy-desferrioxamine D1 2, have been isolated, together with four known hydroxamates, desferrioxamine D1 3, desferrioxamine B 4, desoxy-nocardamine 5 and nocardamine 6, and a diketopiperazine (DKP) 7. The structures of 1–7 were characterized by the analysis of HRESIMS and 1D and 2D NMR data, as well as by comparison with the relevant literature. Three new dehydroxy desferrioxamine derivatives 8–10 were tentatively identified in the molecular network of K. speibonae strain SK5 extracts, and structures were proposed based on their MS/MS fragmentation patterns. A plausible spb biosynthetic pathway was proposed. To the best of our knowledge, this is the first report of the isolation of desferrioxamines from the actinobacterial genus Kribbella.