Metal Ion Chelating Research Articles

A Comprehensive Review on Beneficial Effects of Catechins on Secondary Mitochondrial Diseases.

Mitochondria are the main sites for oxidative phosphorylation and synthesis of adenosine triphosphate in cells, and are known as cellular power factories. The phrase “secondary mitochondrial diseases” essentially refers to any abnormal mitochondrial function other than primary mitochondrial diseases, i.e., the process caused by the genes encoding the electron transport chain (ETC) proteins directly or impacting the production of the machinery needed for ETC. Mitochondrial diseases can cause adenosine triphosphate (ATP) synthesis disorder, an increase in oxygen free radicals, and intracellular redox imbalance. It can also induce apoptosis and, eventually, multi-system damage, which leads to neurodegenerative disease. The catechin compounds rich in tea have attracted much attention due to their effective antioxidant activity. Catechins, especially acetylated catechins such as epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), are able to protect mitochondria from reactive oxygen species. This review focuses on the role of catechins in regulating cell homeostasis, in which catechins act as a free radical scavenger and metal ion chelator, their protective mechanism on mitochondria, and the protective effect of catechins on mitochondrial deoxyribonucleic acid (DNA). This review highlights catechins and their effects on mitochondrial functional metabolic networks: regulating mitochondrial function and biogenesis, improving insulin resistance, regulating intracellular calcium homeostasis, and regulating epigenetic processes. Finally, the indirect beneficial effects of catechins on mitochondrial diseases are also illustrated by the warburg and the apoptosis effect. Some possible mechanisms are shown graphically. In addition, the bioavailability of catechins and peracetylated-catechins, free radical scavenging activity, mitochondrial activation ability of the high-molecular-weight polyphenol, and the mitochondrial activation factor were also discussed.

Interaction mechanism of a novel reagent scheme in the selective separation of scheelite from calcite

Up to now, the selective separation of scheelite and calcite is still tricky. Etidronic acid (abbreviated as EA or H4L) is an environmental scale inhibitor capable of chelating metal ions. This research adopted the EA as a selective depressant to separate scheelite from calcite. Flotation results of the single mineral, binary mixed minerals, and real ore showed that EA had better selectivity for calcite at pH 10.0 with sodium oleate (NaOL) as a collector. Zeta potential results found that EA adsorption amount on the positively charged calcite surfaces was more significant than that on the negatively charged scheelite surfaces. X-ray photoelectron spectroscopy, solution chemistry, and density functional theory (DFT) calculation further proved that on calcite, the active O atoms in the dominant species (HL3-) of EA had a strong chemical interaction with Ca sites to form a hydrophilic Ca–EA complex by O 2 s and Ca 3p orbitals hybrid. In contrast, the interaction with these on scheelite was significantly weaker. Afterward, NaOL tended to occupy the scheelite surfaces due to its higher activity of Ca rather than the calcite surfaces. Therefore, the difference in HL3- and OL- adsorption on both minerals achieved the selective separation of scheelite and calcite.

Alzheimer's Drug PBT2 Interacts with the Amyloid β 1-42 Peptide Differently than Other 8-Hydroxyquinoline Chelating Drugs.

Although Alzheimer's disease (AD) was first described over a century ago, it remains the leading cause of age-related dementia. Innumerable changes have been linked to the pathology of AD; however, there remains much discord regarding which might be the initial cause of the disease. The "amyloid cascade hypothesis" proposes that the amyloid β (Aβ) peptide is central to disease pathology, which is supported by elevated Aβ levels in the brain before the development of symptoms and correlations of amyloid burden with cognitive impairment. The "metals hypothesis" proposes a role for metal ions such as iron, copper, and zinc in the pathology of AD, which is supported by the accumulation of these metals within amyloid plaques in the brain. Metals have been shown to induce aggregation of Aβ, and metal ion chelators have been shown to reverse this reaction in vitro. 8-Hydroxyquinoline-based chelators showed early promise as anti-Alzheimer's drugs. Both 5-chloro-7-iodo-8-hydroxyquinoline (CQ) and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline (PBT2) underwent unsuccessful clinical trials for the treatment of AD. To gain insight into the mechanism of action of 8HQs, we have investigated the potential interaction of CQ, PBT2, and 5,7-dibromo-8-hydroxyquinoline (B2Q) with Cu(II)-bound Aβ(1-42) using X-ray absorption spectroscopy (XAS), high energy resolution fluorescence detected (HERFD) XAS, and electron paramagnetic resonance (EPR). By XAS, we found CQ and B2Q sequestered ∼83% of the Cu(II) from Aβ(1-42), whereas PBT2 sequestered only ∼59% of the Cu(II) from Aβ(1-42), suggesting that CQ and B2Q have a higher relative Cu(II) affinity than PBT2. From our EPR, it became clear that PBT2 sequestered Cu(II) from a heterogeneous mixture of Cu(II)Aβ(1-42) species in solution, leaving a single Cu(II)Aβ(1-42) species. It follows that the Cu(II) site in this Cu(II)Aβ(1-42) species is inaccessible to PBT2 and may be less solvent-exposed than in other Cu(II)Aβ(1-42) species. We found no evidence to suggest that these 8HQs form ternary complexes with Cu(II)Aβ(1-42).

Design Strategies for Responsive Fluorine‐19 Magnetic Resonance Probes Using Paramagnetic Metal Complexes

AbstractMagnetic resonance imaging (MRI) is a powerful and widely used in vivo imaging technique that enables whole body imaging without ionizing radiation. In clinical practice, 1H MRI is employed for imaging anatomical and physiological states via monitoring of protons in water and lipids. In order to monitor biochemical processes at the molecular level, several research groups are exploring responsive MRI agents that alter their signal upon interaction with an analyte or biological environment of interest. Fluorine (19F) MRI agents are promising due to the 19F nucleus having similar magnetic resonance (MR) properties to proton and the absence of endogenous 19F in living systems, resulting in no background signal. In order to make responsive 19F MR agents for molecular imaging and analysis, fluorinated platforms must be developed in which their 19F MR signal changes after interacting with a target analyte. A promising strategy is to use paramagnetic metals to modulate the 19F MR signal by altering the relaxation rates and/or chemical shift of an appended 19F imaging tag. In this concept, we provide an overview of the theoretical principles and molecular design strategies that have been exploited in the design of responsive 19F MR agents, with a specific focus on agents based on small molecule paramagnetic metal ion chelates.

Effect of chelating solubilization via different alkanolamines on the dissolution properties of steel slag

This work aims to investigate the solubilizing ability of alkanolamines on steel slag (SS) and the chelating ability of alkanolamines with metal ions. In this paper, the chelation effect of four alkanolamines, including triethanolamine (TEA), triisopropanolamine (TIPA), diethanol-isopropanolamine (DEIPA), and methyl diethanolamine (MDEA), and metal ions on the dissolution of SS was investigated. The conductivity meter, pH meter, X-ray powder diffraction (XRD), inductively coupled plasma atomic emission spectroscopy (ICP-AES), total organic carbon (TOC) and isothermal calorimetry were used to investigate the solubilizing ability of SS impacted by alkanolamines. Additionally, the conductivity meter and chemical precipitation method (CPM) were used to investigate and explore the chelating ability of alkanolamines interacting with the metal ions. Finally, the nuclear magnetic resonance hydrogen (1HNMR) spectroscopy was adopted to investigate the chelating mechanism between alkanolamines and metal ions. The results showed that the alkanolamines increased the elemental concentrations of [Ca], [Al], [Fe] and [Si] in the liquid phase of SS through chelating and promoted the dissolution of the mineral phase of C3S, C2S and C4AF in SS. Among the different alkanolamines, DEIPA was present in the liquid phase for the longest time and possessed a more sustained ability to chelating metal ions. The result also shows that alkanolamines can chelate the Ca2+, Al3+ and Fe3+ in solution. The chelating ability of tertiary alkanolamines were stronger than the secondary alkanolamine. And the alkanolamine with asymmetric molecular structure have stronger chelating ability than those with symmetric molecular structure. Tertiary alkanolamines form ternary five-ring structure with metal ion through nitrogen and oxygen atoms.

Synergistic bactericidal effect of nisin and phytic acid against Escherichia coli O157:H7

The food industry must prevent food contamination caused by pathogenic Escherichia coli strains as they pose a severe public health threat worldwide and lead to unimaginable economic losses. In this study, the synergistic antibacterial activity in vitro of nisin and phytic acid (PA), a natural metal chelate, against 5 foodborne isolates of E. coli were evaluated by a checkerboard assay. Checkerboard assay showed that nisin and PA showed a synergistic effect (FICI <0.375) on three O157 serogroup strains and an addictive effect (0.5<FICI <0.5625) on the remaining two non-O157 serogroup strains. Then the combined bactericidal effect of these compounds against E. coli O157:H7 was investigated. Results showed the number of planktonic and biofilm cells inactivated in groups treated with a combination of 0.512 mg/mL nisin plus 1 × MIC or 2 × MIC PA was significantly higher than the sum of groups treated alone (P < 0.05). Electron scanning microscopy studies revealed that the nisin plus PA treatment had a severe effect on E. coli O157:H7, which after treatment cell morphology appeared deflated with large invaginations. The effect of nisin plus PA against E. coli O157:H7 was furthermore assessed on cold-stored beef, where a similar synergistic bactericidal effect was observed. The studies demonstrate the great potential of the food-approved nisin to control the growth of undesired E. coli pathogens in foods. We used PA to overcome the permeability barrier of the outer membrane to nisin, but other food-grade metal ion chelators such as polyphosphate most likely could be used as well.

Application of Neuromelanin MR Imaging in Parkinson Disease.

MRI has been used to develop biomarkers for movement disorders such as Parkinson disease (PD) and other neurodegenerative disorders with parkinsonism such as progressive supranuclear palsy and multiple system atrophy. One of these imaging biomarkers is neuromelanin (NM), whose integrity can be assessed from its contrast and volume. NM is found mainly in certain brain stem structures, namely, the substantia nigra pars compacta (SNpc), the ventral tegmental area, and the locus coeruleus. Another major biomarker is brain iron, which often increases in concert with NM degeneration. These biomarkers have the potential to improve diagnostic certainty in differentiating between PD and other neurodegenerative disorders similar to PD, as well as provide a better understanding of pathophysiology. Mapping NM in vivo has clinical importance for gauging the premotor phase of PD when there is a greater than 50% loss of dopaminergic SNpc melanized neurons. As a metal ion chelator, NM can absorb iron. When NM is released from neurons, it deposits iron into the intracellular tissues of the SNpc; the result is iron that can be imaged and measured using quantitative susceptibility mapping. An increase of iron also leads to the disappearance of the nigrosome-1 sign, another neuroimage biomarker for PD. Therefore, mapping NM and iron changes in the SNpc are a practical means for improving early diagnosis of PD and in monitoring disease progression. In this review, we discuss the functions and location of NM, how NM-MRI is performed, the automatic mapping of NM and iron content, how NM-related imaging biomarkers can be used to enhance PD diagnosis and differentiate it from other neurodegenerative disorders, and potential advances in NM imaging methods. With major advances currently evolving for rapid imaging and artificial intelligence, NM-related biomarkers are likely to have increasingly important roles for enhancing diagnostic capabilities in PD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Elite Zingiber extracts as potential free radical scavengers and radioprotectors

ABSTRACT Fresh rhizome extracts of four elite Zingiber species, viz., Zingiber kangleipakense, Zingiber montanum, Zingiber officinale, and Zingiber zerumbet, prepared in 60% aqueous ethanol/60% aqueous methanol solutions were used for assessing their comparative free radical scavenging and radioprotective properties. Various methods, such as ferric ion reducing power assay, DPPH ion scavenging assay, nitric oxide scavenging assay, metal chelating assay, thiyl/sulfur free radical reactivity assay, and hydroxyl ion scavenging assay, were employed for radical scavenging capabilities. Bio-active principles, such as total phenolic, flavonoid, and ascorbic acid contents, were also assessed. Z. officinale showed the highest TPC, TFC, and ascorbic acid content of 650 mg GAE/100 g, 889 mg QE/100 g, and 3.19 mg/100 g, respectively, as well as the greatest efficacy in ferric ion reducing and DPPH scavenging ability having lowest IC50 value of 0.22 mg/mL. Z. montanum showed the lowest IC50 value of 0.91 mg/mL in NO scavenging assay and also exhibited the highest curcumin protection in thiyl free radical scavenging assay. Z. kangleipakense showed the lowest IC50 value of 0.24 mg/mL and 0.25 mg/mL in metal ion chelating assay and hydroxyl radical assay, respectively. 60% aqueous ethanol extracts of Z. officinale and Z. kangleipakense were used for radioprotective assays both for in vitro and in vivo using plasmid pBR322 DNA and bone marrow cells of albino rats, respectively, based on their significant free radical scavenging properties. At the same concentration of 0.25 mg/mL, Z. officinale and Z. kangleipakense showed 71.50% and 56.54% protection, respectively, of DNA from exposure to 6 Gy gamma radiation. Also, Z. officinale and Z. kangleipakense exhibited 51.16% and 38.96% protection from radiation-induced chromosomal damages in rats, respectively, when exposed to 2 Gy. Reduction in the DNA open circular form as well as the chromosomal aberrations in treatments with plant extracts compared to the controls confirmed the radioprotective potentials of the extracts. The results showed that the extracts possessed potential antioxidant compounds having capacities to scavenge radiation-induced free radical species. The accessibility of the extracts in radiation countermeasures can provide immense nutraceutical potentials.

Natural Molecular Mechanisms of Plant Hyperaccumulation and Hypertolerance towards Heavy Metals.

The main mechanism of plant tolerance is the avoidance of metal uptake, whereas the main mechanism of hyperaccumulation is the uptake and neutralization of metals through specific plant processes. These include the formation of symbioses with rhizosphere microorganisms, the secretion of substances into the soil and metal immobilization, cell wall modification, changes in the expression of genes encoding heavy metal transporters, heavy metal ion chelation, and sequestration, and regenerative heat-shock protein production. The aim of this work was to review the natural plant mechanisms that contribute towards increased heavy metal accumulation and tolerance, as well as a review of the hyperaccumulator phytoremediation capacity. Phytoremediation is a strategy for purifying heavy-metal-contaminated soils using higher plants species as hyperaccumulators.

Novel melatonin-trientine conjugate as potential therapeutic agents for Alzheimer’s disease

Researchers continue to explore drug targets to treat the characteristic pathologies of Alzheimer's disease (AD). Some drugs relieve the pathological processes of AD to some extent, but the failed clinical trials indicate that multifunctional agents seem more likely to achieve the therapy goals for this neurodegenerative disease. Herein, a novel compound named melatonin-trientine (TM) has been covalently synthesized with the natural antioxidant compounds melatonin and the metal ion chelator trientine. After toxicological and pharmacokinetic verification, we elucidated the effects of intraperitoneal administration of TM on AD-like pathology in 6-month-old mice that express both the β-amyloid (Aβ) precursor protein and presenilin-1 (APP/PS1). We found that TM significantly decreased Aβ deposition and neuronal degeneration in the brains of the APP/PS1 double transgenic mice. This result may be due to the upregulation of iron regulatory protein-2 (IRP2), insulin degrading enzyme (IDE), and low density lipoprotein receptor related protein 1 (LRP1), which leads to decreases in APP and Aβ levels. Additionally, TM may promote APP non-amyloidogenic processing by activating the melatonin receptor-2 (MT2)-dependent signaling pathways, but not MT1. In addition, TM plays an important role in blocking γ-secretase, tau hyperphosphorylation, neuroinflammation, oxidative stress, and metal ion dyshomeostasis. Our results suggest that TM may effectively maximize the therapeutic efficacy of targeting multiple mechanisms associated with AD pathology.

α-Lipoic Acid Inhibits Apoptosis by Suppressing the Loss of Ku Proteins in Helicobacter pylori-Infected Human Gastric Epithelial Cells.

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the gastric mucosa and triggers various stomach diseases. H. pylori induces reactive oxygen species (ROS) production and DNA damage. The heterodimeric Ku70/Ku80 protein plays an essential role in the repair of DNA double-strand breaks (DSB). Oxidative stress stimulate apoptosis and DNA damage that can be repaired by Ku70/80. However, excessive reactive oxygen species (ROS) can cause Ku protein degradation, resulting in DNA fragmentation and apoptosis. α-lipoic acid (α-LA), which is found in organ meats such as liver and heart, spinach, broccoli, and potatoes, quenches free radicals, chelates metal ions, and reduces intracellular DNA damage induced by oxidative stress. Here, we investigated whether H. pylori decreases Ku70/80 and induces apoptosis, and whether α-LA inhibits changes induced by H. pylori. We analyzed ROS, DNA damage markers (γ-H2AX, DNA fragmentation), levels of Ku70/80, Ku–DNA binding activity, Ku80 ubiquitination, apoptosis indices (Bcl-2, Bax, apoptosis-inducing factor (AIF), and caspase-3), and viability in a human gastric epithelial adenocarcinoma cell line (AGS). H. pylori increased ROS, DNA damage markers, Ku80 ubiquitination, and consequently induced apoptosis. It also decreased nuclear Ku70/80 levels and Ku–DNA-binding activity; increased Bax expression, caspase-3 cleavage, and truncated AIF; but decreased Bcl-2 expression. These H. pylori-induced alterations were inhibited by α-LA. The antioxidant N-acetylcysteine and proteasome inhibitor MG-132 suppressed H. pylori-induced cell death and decreased nuclear Ku70/80 levels. The results show that oxidative stress induced Ku70/80 degradation via the ubiquitin–proteasome system, leading to its nuclear loss and apoptosis in H. pylori-infected cells. In conclusion, α-LA inhibited apoptosis induced by H. pylori by reducing ROS levels and suppressing the loss of Ku70/80 proteins in AGS cells.

Analysis of Antioxidant, Acetylcholinesterase Inhibitory Properties and Chemical Composition of Some Indian Himalayan Species of Berberis: A Comparative Study

Background: Methanolic extracts of the stems of six species of Berberis e.g., Berberis umbellata, B. vulgaris (Syn: B. nepalensis), B. insignis, B. asiatica, and B. aristata were studied for their antioxidant properties and acetylcholinesterase inhibitory properties. Materials and Methods : Antioxidant property was studied in different systems of assay e.g., DPPH radical scavenging assay, superoxide radical scavenging assay, nitric oxide scavenging assay, assay to chelate metal. Acetylcholinesterase (AChE) inhibitory property was measured using AChE from electric eel. Results: It was observed that all the extracts scavenged DPPH, superoxide and nitric oxide radical and chelated metal ion in a dose dependent manner. The antioxidant properties were correlated with total phenol content, total flavonoid content, berberine and palmatine content. The AChE inhibitory activities of the extracts were also correlated well with berberine, palmatine, total phenol and total flavonoid content. A few phenolic compounds were detected by GC-MS. Highest activity in all respect was observed in B. aristata. Conclusion: Methanolic extracts of the stems of B. aristata exhibited the highest antioxidant activity.

Biogenic Synthesis and antibiofilm efficacy of iron nanoparticles via computer simulation

The search for new drugs can be accelerated by in silico methods, i.e., fully computational methods known for their speed and low cost, allowing the analysis of a large amount of data, e.g., thousands of possible antimicrobials, in a few weeks. Molecular docking and first-principles calculations are great allies in this quest. They enable the assessment of protein-ligand interactions and can predict interactions between NPs and macromolecules to provide more information about the interactions and dynamics of NPs in biological systems. In this context, this work aims to use in silico methods to detect the formation of biogenic metallic nanoparticles from functional microalgal biomolecules of the genus Chlorella, which have chelation of metal ions as a fundamental property, and to verify the possible antibacterial biofilm efficacy using computational tools such as molecular docking. In a first analysis, it was found that the iron salt FeSO4 was the most suitable to bind the microalgal enzyme and produce its phytochelatin protein. Following this result, an analysis of the electronic structure of the phytochelatin complex with the iron salt was carried out, proving its structural modification at the nanometric level, after which an analysis of its therapeutic effect on antibiofilm activity was performed. S. aureus, a bacterium known for its multiresistant to antibiotics, these results demonstrate, through alternative in silico methods, the physiological role of phytochelatin from microalgae in the detoxification and bioremediation of metallic contaminants.

Structural Characterization and Antimicrobial Studies of Some New Mixed Ligand Complexes of Lomefloxacin and 3‐(Bromoacetyl)coumarin with Some Metals

AbstractThe interaction of Mn(II) (1), Fe(II) (2), Co(II) (3), Ni(II) (4), Cu(II) (5), and Zn(II) (6) with lomefloxacin (LFX) in the existence of 3‐(bromoacetyl)coumarin (BAC) and NaOH in a 1 : 1 : 1 : 1 molar ratio resulted in the formation of unique mixed ligand metal complexes. The ability of two ligands to chelate metal ions was investigated by elemental analysis, molar conductance, effective magnetic moments FT‐IR, ultraviolet‐visible (UV‐Vis), 1H NMR spectra and thermogravimetric analyses (TG‐DTG). FT‐IR spectra of the complexes suggest that LFX reacted with metal ions as bi‐dentate through pyridone oxygen and carboxylate oxygen. BAC also interacts as bi‐dentate through oxygen of α,β‐unsaturated ketone and oxygen of lactone carbonyl of coumarin. These chelates are electrolytes, according to conductivity experiments, with a 1 : 1 ratio for Mn(II), Fe(II), and Zn(II) and a 1 : 2 ratio for Co(II), Ni(II), and Cu(II). Electronic and magnetic data revealed an octahedral shape for all compounds. The thermodynamic parameters of thermal breakdown processes such as Ea, ΔH*, ΔS* and ΔG* were determined from TG and DTG curves using Coats‐Redfern (CR) and Horowitz‐Metzeger (HM) techniques for LFX, BAC and their metal complexes. The structural geometry of the complexes is confirmed by molecular modeling studies. The findings show that the complexes are soft with regard to ligands, with values ranging from 0.058 eV for Fe(II) complex to 0.090 eV for Zn(II) complex and 11.11 to 17.24 eV for LFX and BAC, respectively, and 0.121, 8.26 eV and 0.111, 9.009 eV for LFX and BAC. The ligands and their complexes were tested in vitro for antibacterial activity against a variety of bacterial and fungal strains, and the results revealed that the complexes had significantly higher potency than the parent drug.

Relationship between the molecular structure of different dithiocarbamates and their oil removal performance.

Six kinds of dithiocarbamates (DTCs) were synthesized from three linear amines with different amino numbers, two polyether amines with different molecular weights, and one branched amine with benzene rings, respectively. The conditions affecting oil removal rate and floc rising time of DTC were studied using simulated oily wastewater. Furthermore, the effects of the molecular structure of DTC on oil removal efficiency, floc morphology, floc rising time, and floc adhesion were investigated. When the conditions were optimal, the oil removal efficiency of DTC synthesized from polyethylene polyamine was 95.14%, which was higher than other DTCs. Meanwhile, the ferrous ion was the most suitable chelating metal ion for DTC than other transition metal ions. The increase of amino groups in the initiators improves the oil removal efficiency of DTC, while the linear structural DTC exhibits a low oil removal efficiency due to a lack of network structural flocs. The introduction of polyether structure helps reduce the volume of the flocs and make them compact, but it also increases the adhesion of the floc on the metal surface. The introduction of bisphenol A phenol amino resin structure induces the generation of the flocs in oil wastewater and improves the oil removal efficiency.

In vitro Screening for Antioxidant and Antimicrobial Properties of 3,5-Bis(E-thienylmethylene) piperidin-4-one, a Curcumin Analogue

Pharmacognosy Research,2022,14,3,276-283.DOI:10.5530/pres.14.3.40Published:July 2022Type:Original ArticleAuthors:Jayaseelan Nivedha, Kaliyamoorthi Kanimozhi, Subashchandrabose Olikkavi, T. Vidhyasagar, Natesan Vijayakumar, Chinnaiyan Uma, K. Rajeswari, and Lakshmanan Vennila Author(s) affiliations:Jayaseelan Nivedha1, Kaliyamoorthi Kanimozhi1, Subashchandrabose Olikkavi1, T. Vidhyasagar2, Natesan Vijayakumar1, Chinnaiyan Uma4, K. Rajeswari2,3, Lakshmanan Vennila1,* 1Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram, Tamil Nadu, INDIA. 2Department of Chemistry, Annamalai University, Chidambaram, Tamil Nadu, INDIA. 3Department of Chemistry, GAC-CDM, Chidambaram, Tamil Nadu, INDIA. 4Department of Microbiology, Annamalai University, Chidambaram, Tamil Nadu, INDIA. Abstract:Background: Curcumin is a naturally occurring bis-chalcone derivative in the commonly used Indian spice turmeric and is well-known for its potent chemopreventive, anti-angiogenic, anti-cancer properties. 3,5-bis[(E)-thienylmethylene] piperidin-4-one (BTMP) is the newly synthesised synthetic analogue of curcumin that is tested for its antioxidant and antimicrobial properties in vitro. Objectives: This study was to determine the antioxidant activity and antibacterial potentials of newly synthesised analogues of curcumin viz., 3,5-bis[(E)- thienylmethylene] piperidin-4-one (BTMP), was examined in vitro. Materials and Methods: BTMP was evaluated for its antioxidant and antimicrobial using 1,1-diphenyl-2-picryl hydroxyl (DPPH•) radical scavenging assay, 2,2’-azinobis3-ethyl benzothiazoline-6-sulfonic acid (ABTS•+), ferric reducing antioxidant power (FRAP), nitric oxide scavenging assay, superoxide anion radical scavenging assay (O2•−), hydrogen peroxide scavenging, reducing ability assay, metal ion chelating and phosphomolybdenum assays. Results: 40μg/ml of BTMP showed higher antioxidant activity than the other three doses due to its highest free radical scavenging ability at this particular dose. All doses of BTMP showed antimicrobial activity against E. coli and S. aureus. 40μg/ml of BTMP showed the highest zone of inhibition against both tested pathogens. Conclusion: The introduction of basic functionality and the presence of exocyclic double bonds of BTMP has significantly contributed to the antioxidant activity and antimicrobial activity against both gram-positive and gram-negative bacteria. Keywords:Antibacterial, Antioxidant, Curcumin, DPPH, Reducing abilityView:PDF (361.28 KB)

Design, Structural Inspection and Bio-Medicinal Applications of Some Novel Imine Metal Complexes Based on Acetylferrocene.

Some novel imine metal chelates with Cr3+, Mn2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, and Cd2+ cations were produced from 2-acetylferrocene and 3-aminophenol. The new acetylferrocene azomethine ligand ((Z)-cyclopenta-1,3-dien-1-yl(2-(1-((3-hydroxyphenyl)imino)ethyl)cyclopenta-2,4-dien-1-yl)iron) and its metal ion chelates were constructed and elucidated using FT-IR, UV/Vis, 1HNMR, DTA/TGA, CHNClM studies, mass spectrometry and SEM analysis. According to the TGA/DTG investigation, the ferrocene moiety spontaneously disintegrates to liberate FeO. The morphology of the free acetylferrocene azomethine via SEM analysis was net-shaped with a size of 64.73 nm, which differed in Cd(II) complex to be a spongy shape with a size of 42.43 nm. The quantum chemical features of the azomethine ligand (HL) were computed, and its electronic and molecular structure was refined theoretically. The investigated acetylferrocene imine ligand behaves as bidinetate ligand towards the cations under study to form octahedral geometries in case of all complexes except in case of Zn2+ is tetrahedral. Various microorganisms were used to investigate the anti-pathogenic effects of the free acetylferrocene azomethine ligand and its metal chelates. Moreover, the prepared ligand and its metal complexes were tested for anticancer activity utilizing four different concentrations against the human breast cancer cell line (MCF7) and the normal melanocyte cell line (HBF4). Furthermore, the binding of 3-aminophenol, 2-acetylferrocene, HL, Mn2+, Cu2+, and Cd2+ metal chelates to the receptor of breast cancer mutant oxidoreductase was discovered using molecular docking (PDB ID: 3HB5).

Anti-Inflammatory Activity of Mulberry Leaf Flavonoids In Vitro and In Vivo.

Mulberry (Morus alba L.) is a flowering tree traditionally used in Chinese herbal medicine. Mulberry leaf flavonoids (MLFs) have been reported to exert important anti-inflammatory and antioxidant properties. The purpose of this study was to select the MLF with the best anti-inflammatory and antioxidative activities from MLFs eluted by different ethanol concentrations (30%, 50%, and 75%) and explore its pharmacological properties. Three types of MLFs inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory cytokines in lipopolysaccharide (LPS)-induced RAW 264.7 cells. All MLFs boosted the antioxidative capacity by decreasing the reactive oxygen species (ROS) production and the scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and improving the metal ion chelating activity and reducing power. The results revealed that the MLFs eluted by 30% ethanol exhibited the best anti-inflammatory and antioxidative activities. A nontargeted metabolomic analysis was used to analyze 24 types of differential flavonoids between the MLFs. Quercetin, kaempferol, and their derivatives in 30%MLF were more abundant than the other two MLFs. Furthermore, we evaluated the pharmacological activities of 30%MLF in dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) mice. The 30%MLF could alleviate the clinical symptoms, reduce the secretion of inflammatory cytokines, and inhibit the activation of the inflammatory pathway in DSS-induced colitis mice. This study will provide valuable information for the development of MLFs eluted by 30% ethanol as a functional food.

Effect of solvent concentrations on antioxidant activity and biochemical parameters of adzuki bean (Vigna angularis) sprouts at different germination times

In this study were determined DPPH radical scavenging power, metal-ion chelating activity, gamma aminobutyric acid and phytic acid levels, total phenolic substance content, extraction yield in water and various organic solvents (acetone, n-hexane and ethanol), concentrations (50, 70 and 90%) and germination times (0, 24, 48, 72, 96 and 120 h) of adzuki bean (Vigna angularis) sprouts. The extraction yield ranged from 11.47% (H3) to 28.55% (E1). The highest DPPH radical scavenging capacity was determined at E2 concentration (2.978 µmol/g DW) for 120 h (P&amp;lt;0.05). E3 (1.744 mg EDTA equivalent/100 g) and A3 (1.145 mg EDTA equivalent/100 g) showed the highest metal chelating activity after 48h of germination. This activity decreased in the germination period from 48 h to 120 h (P&amp;lt;0.05). When different solvent concentrations were compared no significant change (P&amp;gt;0.05) in gamma aminobutyric acid and phytic acid contents at 0, 24 and 48 h analyses. The highest gamma aminobutyric acid content was detected to A1 (67.29 mg/100 g DW) and H1 (69.17 mg/100 g DW) concentrations at 120 h (P&amp;lt;0.05). No significant changes were found in total phenol content in all solvent concentrations in 48 h (P&amp;gt;0.05). At the end of 120 h, total phenolic components were determined in the lowest levels in W and the highest concentrations in E2 (P&amp;lt;0.05). These results showed that adzuki bean seeds may be more effective in these parameters, depending on the increase in the activities of bioactive components and the decrease in anti-nutritional factors, and the concentration in water and aqueous organic solvents with the increase of germination time.

High-throughput detection of metal contamination in HTS outputs.

Large compound libraries utilised for HTS often include metal contaminated compounds which can interfere with assay signal or target biology, and therefore appear as hits. Pursuit of these compounds can divert considerable time and resource away from more propitious hits, yet there is currently no established method of detecting metal impurities in a rapid and effective manner. Here we describe the development and application of a high-throughput method to identify metal contaminants using acoustic mist ionisation mass spectrometry (AMI-MS). Although metals species by themselves are not detectable by AMI-MS, we have identified two compounds that chelate metal ions and enable their detection. 6-(diethylamino)-1,3,5-triazine-2,4(1H,3H)-dithione (DMT) and 1-(3-{[4-(4-cyanophenyl)-1-piperidinyl]carbonyl}-4-methylphenyl)-3-ethylthiourea (TU) can form complexes with a range of metal ions. Using a collection of metal catalysts, we have developed two metal chelator assays that collectively allow for the detection of Ag, Au, Co, Cu, Fe, Pd, Pt and Zn. We employed these assays to profile the hit outputs of a Zn liable target, and a Pd liable target, and identified significant quantities of metal contaminated compounds in the HTS outputs. This work provides a method of rapidly identifying metal impurities in hit compounds and has become part of an established workflow in triaging HTS outputs at AstraZeneca, facilitating faster identification of robust lead series.