Potent Chelator Research Articles

Design, synthesis, metal chelation potential and biological evaluation of pyridine chalcones as multi-target-directed ligands against Alzheimer's disease

Two sets of 1-phenyl-3-(pyridinyl) prop‑2-en-1-one analogs, 7a-d and 8a-d were designed by the incorporation of pyridine and chalcone privileged scaffolds with the objective of developing multifunctional molecules for Alzheimer's disease (AD). The structure-based approach was used to evaluate the binding potential of the designed pyridine chalcone series in acetylcholinesterase, prior to synthesis. The hybrid molecules designed from the amalgamation of two privileged scaffolds demonstrated excellent potential for simultaneous inhibition of acetylcholinesterase (AChE) and amyloid beta (Aβ1–42) aggregation in addition to promising radical scavenging activities, metal-chelating properties and inhibitory potential for attenuation of advanced glycation products. The compounds showed mixed inhibition of AChE in enzyme kinetic studies with the most potent compound 8c showing an IC50 value of 0.1 ± 0.01 μM. Compounds of both series exhibited good potential of inhibiting Aβ1–42 aggregation, with compound 8c exhibiting an inhibitory potential of 83.58% after 48 h. The molecules demonstrated moderate to good radical scavenging activity in both DPPH and H2O2 radical scavenging assays, moderate inclination for metal chelation and significant potential to inhibit formation of advanced glycation products. The mechanistic basis of these actions has been probed by experimental and computational techniques that leads to greater understanding of the underlying structural basis for the activities of these promising molecules for holistic treatment of AD. Taken together, this work reveals the multifaceted pleiotropy of the designed molecules, especially the 4-pyridine analogs, with the compounds 8b and 8c demonstrating excellent potential as multi-target directed ligands to address most of the causative pathologies of AD.

Comparative Analysis of Alternative Calcium Chelators for the Treatment of Calcific Band Keratopathy.

In this study, we compared clinically relevant biochemical properties of each chelator for pH, osmolarity, and calcium chelation potential. In total, 0.2 M K 2 EDTA and K 3 EDTA (BD vacutainer tubes by Becton, Dickinson and Company) and Na 2 EDTA (Sigma Aldrich) solutions were made. The pH of each solution was measured (Mettler Toledo pH meter), and the theoretical osmolarity was calculated. Next, we determined the calcium chelation potential of each EDTA salt by titrating it with 10 μmol of calcium hydroxyapatite or CaCl 2 containing Patton-Reeder colorimetric indicator. Statistical significance was analyzed using analysis of variance. The 0.2 M solutions of Na 2 EDTA, K 2 EDTA, and K 3 EDTA have pH values of 4.43, 5.71, and 9.191 and theoretical osmolarities of 600, 600, and 800 mOsm/L, respectively. Calcium chelation ability was similar among all 3 solutions: 0.94 to 0.98 mol of EDTA was needed to fully chelate 1 mol calcium ions of CaCl 2 ( P = 0.296), 0.100 to 0.108 mol of EDTA for 1 mol calcium ions of the hydroxyapatite aqueous suspension ( P = 0.296), and 0.992 to 0.996 mol for 1 mol calcium ions of hydroxyapatite in acidic solution ( P = 0.178). Compared with the clinical standard of 3% (30 mg/mL) Na 2 EDTA, approximately 3.3% (33 mg/mL) K 2 EDTA and 3.6% (36 mg/mL) K 3 EDTA are needed to chelate an equivalent amount of calcium. In this article, we provide clinically relevant biochemical properties of 2 alternatives to Na 2 EDTA and demonstrate comparable calcium chelation ability among all 3 solutions. In situations where sterile sources of Na 2 EDTA are unavailable, potassium EDTA may provide a convenient and equally effective method of treatment for band keratopathy.

Metal Chelators as Anticancer Approach: Part I; Novel 7-Anisidine Derivatives with Multidentate at 7-8 Carbons of Fluoroquinolone Scaffold as Potential Chelator Anticancer and Antilipolytic Candidates

Background: Cancer is one of the greatest troubling maladies currently. It is believed that it is the second reason for death following cardiovascular maladies. Owing to the multiplicity of its types, stages and genetic basis, there is no existing drug to cure all types of cancer. Resistance to present drugs and severe adverse effects are other challenges in the struggle against cancer. In such pursuit, fluoroquinolones (FQs) have the potential as antiproliferative compounds due to safety, low cost, and absence of resistance.
 Aims: In this study, we aim to synthesize biologically active compounds that have dual anticancer and anti-lipase potential. Sixteen compounds were prepared, fully characterized, and studied through identification of IC50 values against the highly susceptible cancer cell lines.
 Methods: In this work we are concerned with synthesizing biologically active compounds that belong to fluoroquinolones (FQs) with dual anti-colorectal cancer and anti-lipase activity, owing to association between cancer and obesity, conduct titration and docking experiments to validate our hypothesis.
 Results: In vitro findings indicated that these compounds demonstrated promising anticancer activity against tested cell lines in micromolar range with a potency comparable to cisplatin. Compound 11 exhibited approximately doubled potency compared to cisplatin against SW620 colorectal cancer cell line with IC50 3.2 μM which proposes FQs as potent antiproliferative agents. The synthesized Fluoroquinolone (FQ) compounds were further screened for their in vitro anti-lipase potential. The findings demonstrated that all the screened compounds have demonstrated remarkable anti-lipase activity, as compared to control molecule orlistat. Compound 9 exhibited comparable activity to orlistat against pancreatic lipase with IC50 0.4 μM which proposes FQs as potent pancreatic lipase inhibitors.
 Conclusions: The anticancer potential of these derivatives is referred to their ability to inhibit Topo II which indicates that chelation is the mechanism of inhibition of Topo II emphasized with titration and docking experiments.

Competitive recovery of copper ions using ethyl acetoacetate modified chitosan/organo-functionalized alginate hydrogel beads: kinetics and isothermal sorption studies

Surface functionalization of chitosan using some chelating ligands not only improves sorption capacity but also induces selectivity into the biopolymer. The current study is based on the facile synthesis of ethyl acetoacetate modified chitosan and surface-functionalized alginate composite beads (EAA-MCSA). Chemical modification of sodium alginate was carried out to graft amino thiocarbamate moiety (-OCSNHNH2) to entrench selectivity and specificity across the linear chains of preliminary polysaccharide. Biosorbent (EAA-MCSA) was thoroughly characterized by FT-IR and SEM analysis and employed in the form of composite hydrogel beads for competitive Cu(II) recovery. Newly grafted aminothiocarbamate (-OCSNHNH2) and 1,3-dicarbonyl moieties (-COCH2CO-) are supposed to act as potential chelating sites for enhanced Cu(II) sorption. Kinetic data could be well depicted using pseudo-second order rate law (R2 = 0.99, qexp≈qe,th = 85.25 mg/g, k2 = 0.45–1.17 ×10−2 g/mg.min−1) and sorption data was found in close agreement with Langmuir adsorption isotherm (R2 = 0.99, qm= 390.21 mg/g at 298 K and pH = 6.0, KL= 0.44–0.49 ×10−2 L/mg). The ΔG° values (−20.75, −21.10, −21.30 and −21.50 kJ/mol) and positive ΔH° (−7.63 kJ/mol) designated the sorption process as spontaneous and exothermic, respectively. Hence, EAA-MCSA could be a better sorbent for adsorptive remediation of Cu(II) from dilute effluents.

Toxicity of copper and zinc alone and in combination in Caenorhabditis elegans model of Huntington's disease and protective effects of rutin

Copper (Cu) and Zinc (Zn) are required in small concentrations for metabolic functions, but are also toxic. There is a great concern about soil pollution by heavy metals, which may exposure the population to these toxicants, either by inhalation of dust or exposure to toxicants through ingestion of food derived from contaminated soils. In addition, the toxicity of metals in combination is questionable, as soil quality guidelines only assess them separately. It is well known that metal accumulation is often found in the pathologically affected regions of many neurodegenerative diseases, including Huntington's disease (HD). HD is caused by an autosomal dominantly inherited CAG trinucleotide repeat expansion in the huntingtin (HTT) gene. This results in the formation of a mutant huntingtin (mHTT) protein with an abnormally long polyglutamine (polyQ) repeat. The pathology of HD results in loss of neuronal cells, motor changes, and dementia. Rutin is a flavonoid found in various food sources, and previous studies indicate it has protective effects in HD models and acts as a metal chelator. However, further studies are needed to unravel its effects on metal dyshomeostasis and to discern the underlying mechanisms. In the present study, we investigated the toxic effects of long-term exposure to copper, zinc, and their mixture, and the relationship with the progression of neurotoxicity and neurodegeneration in a C. elegans-based HD model. Furthermore, we investigated the effects of rutin post metal exposure. Overall, we demonstrate that chronic exposure to the metals and their mixture altered body parameters, locomotion, and developmental delay, in addition to increasing polyQ protein aggregates in muscles and neurons causing neurodegeneration. We also propose that rutin has protective effects acting through mechanisms involving antioxidant and chelating properties. Altogether, our data provides new indications about the higher toxicity of metals in combination, the chelating potential of rutin in the C. elegans model of HD and possible strategies for future treatments of neurodegenerative diseases caused by the aggregation of proteins related to metals.

Comprehensive Assessment of the Antioxidant and Anticancer Potential of Selected Ethnobotanical Plants

Globally, among different types of cancers, breast cancer is identified as the chief cause of mortality among females, and it is a challenge to find new effective treatment strategies with minimal side effects and increased efficacy. Plants are an integral part of the traditional indigenous healthcare system and are becoming the concrete source of new drug discovery. Thus, there is a need to obtain a scientific basis for applying traditionally used plants in cancer treatments that may harbour novel phytochemicals. Therefore, this study aims to investigate the antioxidant and anticancer potential of selected plants of ethnobotanical importance. Five plants of ethnobotanical importance were selected and screened to determine their antioxidant potential through various in vitro free radical scavenging assays (such as DPPH, ABTS, hydroxyl, and superoxide radical scavenging), ferric chelation, and total antioxidant potential, and the total phenolic and flavonoid content was estimated for the selected plants. In contrast, the anticancer potential of crude plant extracts was assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) against different breast cancer (MCF-7, MDA-MB-231, and MDA-MB-435S) and hepatic cancer cell lines (HepG2), and human PBMCs (peripheral blood mononuclear cells) were used for toxicity studies. The MTT results showed that among all of the crude plant extracts (CAN = Etlingera linguiformis, SES = Sesbania grandiflora, LEX = Smilax ovalifolia, DES = Desmodium triflorum, and CA = Chenopodium album), it was CAN and LEX that showed the best cytotoxic potential on exposed breast cancer cell lines in contrast to SES, DES, and CA. In addition, at the selected dosages that were exposed to breast cancer cells, none of the extracts from any of the five plants showed any cytotoxicity against human PBMCs. Thus, the crude extracts can be explored further for chemopreventive and anticancer activity on murine models to understand their underlying mechanism for effective cancer management.

Clinical Outcomes of the Deleterious Effects of Aluminum on Neuro-Cognition, Inflammation, and Health: A Review.

Introduction: In the scenario of metal toxicity, aluminum (Al) stands out as a ubiquitous type of metal that can be combined with other elements and form different compounds. Al is widely used daily as an adjuvant in vaccines, antacids, food additives (as components of AI-containing food additives), skin care products, cosmetics, and kitchenware, and can be an element or contaminant present in our daily life. Objective: To present a review of the main deleterious effects of Al on human health. Methods: The search was carried out from September 2022 to February 2023 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases, using scientific articles from 2012 to 2023. The quality of the studies was based on the GRADE instrument, and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusions: A total of 115 files were search returned. Further, 95 articles were evaluated, and 44 were included in this review. Based on the results, measuring Al's relevance to health is essential in medicine. Several studies have demonstrated clinical outcomes and metabolic alterations with Al exposure. The tolerable weekly intake established by the European Food Safety Authority (EFSA) of 1 mg Al/kg body weight can be achieved through dietary exposure alone. Proven neurotoxicity in humans is the critical adverse effect of Al. A carcinogenic effect of Al has not been proven so far. Preventive medicine advocates that exposure to Al should be kept as low as possible. Chelating agents, such as calcium disodium ethylene diamine tetraacetic acid and deferoxamine, are options for acute poisoning, and monomethysilanetriol supplementation may be a long-term strategy with chelation potential. Further studies are needed to assess the impacts of Al on human health.

Michael addition of P-nucleophiles to azoalkenes provides simple access to phosphine oxides bearing an alkylhydrazone moiety.

β-Hydrazonophosphine oxides are precursors of useful organophosphorus compounds, including phosphorylated N-heterocycles, α-aminophosphonates, and vinylphosphonates. In this work, a general transition metal-free synthesis of β-hydrazonophosphine oxides was developed. The method relies on the Michael addition of phosphine oxides R2P(O)H to reactive azoalkenes (1,2-diaza-1,3-butadienes), which are generated in situ from α-halohydrazones and Hunig's base. The reaction stereoselectively leads to Z-isomers of β-hydrazonophosphine oxides that are stabilized by intramolecular hydrogen bonding. The conversion of the products thus obtained into potential chelating ligands was showcased.

Phytochemical and biological activity profiles of Thymbra linearifolia: An exclusively native species of Libyan Green mountains

Thymbra linearifolia, a Green Mountain endemic Libyan plant species belonging to the family Lamiaceae, was investigated as the plant's first documented phytochemical and biological evaluation report.The plant is used for bronchitis, cough, asthma, and gastrointestinal ailments, including dyspepsia, colic pain, and diarrhea.The phenolic and flavonoid contents of T. linearifolia were analyzed qualitatively and quantitatively by LC-MS analysis and spectrophotometric assays. These analyses revealed the presence of 60.67 mg/g of GAE (Gallic Acid Equivalents) and 26.79 mg/g of RE (Rutin Equivalents) of the phenolics and flavonoids, respectively, in the aerial parts of the plants’ ethanolic extract. Cyanidin-3-O-rutinoside (2.26 %), pelargonidin-3-O-rutinoside (2.36 %), gallocatechin (2.94 %), taxifolin (1.22 %), kaempferol-3-O-rutinoside (0.81 %), quercetin-3-O-retinosie (1.20 %), luteolin (0.99 %), apigenin (2.0 %), dimethoxy luteolin (2.97 %), and pinobanksin-3-O-acetate (2.56 %) were detected to be the major flavonoids, whereas the syringic acid hexoside (1.38 %), and rosmarinic acid (2.54 %) were among the most abundant phenolic acids in the plant’s extract. The DPPH scavenging activity was measured at an IC50 value of 34.48 μg/mL. In addition,potential reducing, metal chelating, and free radical scavenging potentials were exhibited in the in vitro assays, i.e., ABST, ORAC, FRAP, and MC. The remarkable antioxidant activity of the plant was attributed to its phenolic and flavonoid contents. The plant extract had strong cytotoxic effects on three types of cancer cell lines, i.e., MCF-7, HepG2, and Panc-1, with IC50 values of 24.023, 22.94, and 33.30 μg/mL, respectively. Furthermore, the plant extract also exhibited cytotoxic effects greater than the standard anticancer drug, doxorubicin, against all the tested cell lines. The in-silicobinding studies also demonstrated that the phytochemical constituents of T. linearifolia have a high binding affinity against the epidermal growth factor receptor (EGFR) protein, which supported the anticancer potentials of the plant.The antimicrobial assay conducted with the well-diffusion method revealed the moderate effects of the plant’s extract against Bacillus subtilis, Staphylococcus aureus, Saccharomyces cerevisiae, and Candida albicans. However, weak antimicrobial effects were recorded against the Gram-negative bacteria, Escherichia coli, and Salmonella typhimurium. These findings corroborated the immense health benefits of the plant, and substantiatedthe medicinal value claims of the plant, which is currently under use in different forms as part of the locals’ folk-medicinal chest.

Evaluating chelating agents and their effects on cellulosic pulps during P-stage bleaching. Part 1: analytical method development

During peroxide bleaching of pulp (“P-stage”), the heavy metal ions must be removed from the pulp and inactivated by chelation before the bleaching to prevent undesired degradation of cellulose by reactive oxygen species. Ethylenediaminetetraacetic acid (EDTA) is mostly used as a chelating agent; however, it may soon be banned because of environmental concerns. Therefore, there is a demand for new chelating agents to replace EDTA, and a comprehensive analytical method is necessary to investigate their chelating ability and the effects on the pulp. In this study, an analytical sequence for evaluating chelating agents and oxidative damage to cellulose during chelation (Q-stage) and bleaching (P-stage) has been established and optimized. GPC provides the molar mass distribution and oxidative damage (as profiles of carbonyl groups relative to the molar mass distribution), and the metal content of the pulp was determined by ICP-OES. This method enables the analysis of the chelating potential of new chelating agents, with simultaneous determination of the impact on cellulose on a molecular level.Graphical abstract

Phytochemical Investigation and in Vitro Antioxidant Activity of Panchavalkala Bark Extracts

Natural antioxidants have an important role in the prevention of many age-related diseases and promotion of health. Among natural antioxidants from plants, flavonoids and other phenolic compounds are potent antioxidants and chelating agents. Panchavalkala the barks of five trees i.e. Nyagrodha (Ficus benghalensis L.), Udumbara (Ficus racemosa L.), Ashwatha (Ficus religiosa L.), Plaksha (Ficus virens Aiton) and Parisha (Thespesiapopulnea (L.)Sol.ex Correa) are also known as Pancha Ksheeri Vrikshas in use since Vedic period. Barks of these trees are dried in shade and are used for different formulations (Pancha Kashaya Kalpanas), in different pathological conditions, especially as wound healing, gynecological disorders and etc. The plant samples were extracted using ethanol and water, and subjected for the phytochemical analysis. It was confirmed that samples contain many biologically active compounds like flavonoids, polyphenols, tannins, alkaloids, glycosides and terpinoids etc. The marker compound of each trial drug and the quantitative analysis has been carried out by high performance liquid chromatography. The antioxidant study was done by using in vitro method 1, 1­-diphenyl-2-picryl-hydrazyl (DPPH) radicle scavenging assay. The marker compounds caffeic acid and gallic acid were quantified in each extract for their quality and efficacy. PVK barks showed high free radicle scavenging activity as evidenced by the low IC50 values in DPPH (EE PVK- 20.46 µg/ml, AE PVK-37.79 µg/ml, EE T.poulenea-22µg/ml, AE T. poulenia- 23.31µg/ml AE F. benghalensis- 25.53µg/ml, EE F. benghalensis- 26.23µg/ml, EE F. religiosa – 34µg/ml). Quercetin- IC50 value 4.026µg/ml is used as standard.
 The results of the study demonstrated that PVK barks possess phyto-constituent’s viz. tannins, flavonoids, polyphenols etc. and has potential antioxidant activity. Thus these barks have good therapeutic potential as natural antioxidant and might be used in life style related conditions like hyperlipidemia, diabetes, obesity, cardiovascular disorders and etc.

Chelation Behaviors of 3,4,3-LI(1,2-HOPO) with Lanthanides and Actinides Implicated by Molecular Dynamics Simulations.

The hydroxypyridinone ligand 3,4,3-LI(1,2-HOPO) (denoted as t-HOPO) is a potential chelator agent for decorporation of in vivo actinides (An), while its coordination modes with actinides and the dynamics of the complexes (An(t-HOPO)) in aqueous phase remain unclear. Here, we report molecular dynamics simulations of the complexes with key actinides (Am3+, Cm3+, Th4+, U4+, Np4+, Pu4+) to study their coordination and dynamic behaviors. For comparison, the complexation of the ligand with a ferric ion and key lanthanides (Sm3+, Eu3+, Gd3+) was also studied. The simulations show that the nature of metal ions determines the properties of the complexes. The t-HOPO in the FeIII(t-HOPO)1- complex ion formed a compact and rigid cage to encapsulate the ferric ion, which was hexa-coordinated. Ln3+/An3+ cations were ennea-coordinated with eight ligating oxygen atoms from t-HOPO and one from an aqua ligand, and An4+ cations were deca-coordinated with a second aqua ligand. The t-HOPO shows strong affinity for metal ions (stronger for An4+ than Ln3+/An3+) benefited from its high denticity and its flexible backbone. Meanwhile, the complexes displayed different dynamic flexibilities, with the AnIV(t-HOPO) complexes more significant than the others, and in the AnIV(t-HOPO) complexes, the fluctuation of the t-HOPO ligand was highly correlated with that of the eight ligating O atoms. This is attributed to the more compact conformation of the ligand, which raises backbone tension, and the competition of the aqua ligand against the t-HOPO ligand in coordinating with the tetravalent actinides. This work enriches our understanding on the structures and conformational dynamics of the complexes of actinides with t-HOPO and is expected to benefit the design of HOPO analogues for actinide sequestering.

Removal of Ferrous using Citric Acid in Patchouli Oil Purification by Complexometry

This study is aimed to examine citric acids as a potential chelating agent to decrease colloidal impurities in patchouli oil to improve its quality. It covers colour, specific density, refractive index, acid value, iron content, oleoresin oil content, and patchouli alcohol. Complete Randomized Design with factorial design is used with two factors and repeated 3 times. Factors are (1) citric acid concentration consists of 0.25%, 0.5%, 1.0% and 1.50% (w/v), (2) stirring time of 30, 60 and 90 minutes. Further, purified oil by citric acid was compared to purified oil by Ethylene Diamine Tetra Acetate (EDTA). Findings show that the concentration of chelating agents and the time of stirring have an effect on the quality of patchouli oil. The higher the chelating concentration and the more the stirring time, the better the quality of purified patchouli oil in terms of colour, specific density, refractive index, acid value, and iron content. Findings also show that citric acid has almost the same performance as EDTA. The main components in patchouli oil (patchouli alcohol and oleoresin oil) are not affected by treatment. Purified patchouli oil by using citric acid meets Indonesian National Standard (SNI) requirements so citric acid is one of the potential chelating agents.

The fatty acid composition, phytochemicals and antioxidant potential of wild edible Smilax excelsa L. shoots.

The present study examines the fatty acid composition, phytochemicals content and antioxidant potential of Smilax excelsa L. shoots, which grows spontaneously and is consumed as food in rural areas of Düzce (Türkiye) province, was investigated. DPPH, ABTS and OH radical scavenging tests were utilized to put forth the antiradical properties of the extracts of this plant. In addition, the metal chelating potential of this plant was also evaluated. The higher the inhibition % value calculated in these tests, the higher the antioxidant activity was considered and the results were evaluated. The average ABTS radical cleaning test results of Smilax excelsa extracts prepared in different concentrations of methanol, ethanol and pure water were found to be 98.14%, 98.16%, 90.20%, respectively. The average DPPH radical cleaning test results of the extracts of this plant prepared in different concentrations of methanol, ethanol and pure water were determined as 87.48%, 76%, 46.53%, respectively. The OH radical cleaning test results of methanol, ethanol and pure water extracts of the Smilax excelsa were determined as 54.79%, 72.54%, none, respectively. In addition, the metal chelation test results of methanol, ethanol and pure water extracts of this plant were determined as 87.26%, 89.36%, 53.70%. The highest protein (85.91 mg BSA/g), proanthocyanidin (55.39 mg CE/g) and phenolic (4957.57 μg GAE/g) content of Smilax excelsa pure water extract was determined. It has been determined that gallic acid (117.33 μg/g), vanillic acid (33.89 μg/g), caffeic acid (4.55 μg/g), ferulic acid (93.78 μg/g), rosmarinic acid (0.33 μg/g) and hydrocynamic acid (0.33 μg/g) are found in different proportions in the Smilax excelsa. It has been stated that Smilax excelsa is an important source of palmitic acid (20.52%), stearic acid (4.95%), oleic acid (4.74%), linoleic acid (20.99%), γ-linolenic acid (2.26%), alpha-linolenic acid (34.29%) and docosahexaenoic acid (2.79%). It has been found that this plant has a low content of fat-soluble vitamins and phytosterols, with the exception of β-sitosterol (6.43μg/g).

New Insights into the Phytochemical Profile and Biological Properties of Lycium intricatum Bois. (Solanaceae)

This work aimed to boost the valorisation of Lycium intricatum Boiss. L. as a source of high added value bioproducts. For that purpose, leaves and root ethanol extracts and fractions (chloroform, ethyl acetate, n-butanol, and water) were prepared and evaluated for radical scavenging activity (RSA) on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, ferric reducing antioxidant power (FRAP), and metal chelating potential against copper and iron ions. Extracts were also appraised for in vitro inhibition of enzymes implicated on the onset of neurological diseases (acetylcholinesterase: AChE and butyrylcholinesterase: BuChE), type-2 diabetes mellitus (T2DM, α-glucosidase), obesity/acne (lipase), and skin hyperpigmentation/food oxidation (tyrosinase). The total content of phenolics (TPC), flavonoids (TFC), and hydrolysable tannins (THTC) was evaluated by colorimetric methods, while the phenolic profile was determined by high-performance liquid chromatography, coupled to a diode-array ultraviolet detector (HPLC-UV-DAD). Extracts had significant RSA and FRAP, and moderate copper chelation, but no iron chelating capacity. Samples had a higher activity towards α-glucosidase and tyrosinase, especially those from roots, a low capacity to inhibit AChE, and no activity towards BuChE and lipase. The ethyl acetate fraction of roots had the highest TPC and THTC, whereas the ethyl acetate fraction of leaves had the highest flavonoid levels. Gallic, gentisic, ferulic, and trans-cinnamic acids were identified in both organs. The results suggest that L. intricatum is a promising source of bioactive compounds with food, pharmaceutical, and biomedical applications.

Oral acetylated whey peptides (AWP) as a potent antioxidant, anti-inflammatory, and chelating agent in iron-overloaded rats' spleen

Excessive iron accumulation is highly toxic to various tissues. Acetylated whey peptides (AWP) obtained from bovine milk have a powerful iron chelating and immunomodulation effect. This study was performed on iron overload (IO)-induced rats' spleen model and announced that AWP can act as a potent prophylactic, natural, affordable, oral and safe iron chelator and can be used as an alternative to the current synthetic drugs. Moreover, it can alleviate oxidative stress and downregulate the proinflammatory markers. The results showed that AWP significantly decreased serum iron, splenic ferritin, oxidative stress markers (ROS, iNOS, and HO-1), and inflammatory markers (IL-6, IL-1β, and NF-κB). Histopathological examination declared that AWP reduced splenic iron deposition and improved histopathological changes in iron-overloaded rats. Immunohistochemical examination showed a significant decrease in macrophage markers (CD68 and CD163) expressions. The efficacy of AWP was compared to that of N-Acetyl-l-cysteine (NAC) and both of them showed no significant difference.

Challenges and Opportunities of Metal Chelation Therapy in Trace Metals Overload-Induced Alzheimer's Disease.

Essential trace metals like zinc (Zn), iron (Fe), and copper (Cu) play an important physiological role in the metabolomics and healthy functioning of body organs, including the brain. However, abnormal accumulation of trace metals in the brain and dyshomeostasis in the different regions of the brain have emerged as contributing factors in neuronal degeneration, Aβ aggregation, and Tau formation. The link between these essential trace metal ions and the risk of AD has been widely studied, although the conclusions have been ambiguous. Despite the absence of evidence for any clinical benefit, therapeutic chelation is still hypothesized to be a therapeutic option for AD. Furthermore, the parameters like bioavailability, ability to cross the BBB, and chelation specificity must be taken into consideration while selecting a suitable chelation therapy. The data in this review summarizes that the primary intervention in AD is brain metal homeostasis along with brain metal scavenging. This review evaluates the impact of different trace metals (Cu, Zn, Fe) on normal brain functioning and their association with neurodegeneration in AD. Also, it investigates the therapeutic potential of metal chelators in the management of AD. An extensive literature search was carried out on the "Web of Science, PubMed, Science Direct, and Google Scholar" to investigate the effect of trace elements in neurological impairment and the role of metal chelators in AD. In addition, the current review highlights the advantages and limitations of chelation therapies and the difficulties involved in developing selective metal chelation therapy in AD patients.

CARNOSINE-LOADED ORAL NIOSOMES AMELIORATE HIGH-FRUCTOSE-INDUCED METABOLIC SYNDROME IN RATS VIA MODULATION OF SIRT1, A METABOLIC MASTER SWITCH

Metabolic syndrome is a crucial health challenge, and the available therapeutic agents are still not effective. Carnosine, a cytoplasmic dipeptide, is a potent anti-glycation, anti-oxidant, anti-inflammatory and chelating agent. However, whether carnosine would be assumed as a potential hypoglycemic agent or not, no decisive report with detailed mechanisms is found yet. As such, we suggest the carnosine-loaded in niosomes as a prospective solution to bypass its unwanted fast degradation by carnosinase which is considered as a major obstacle with the clinical application of carnosine as an oral drug therapy. Toward this, the purpose of our study is to assess the profits of oral administration of carnosine, and carnosine-loaded niosome in HFD-induced metabolic syndrome rats and to inspect some of the involved mechanisms. Initially, carnosine-loaded niosomes were prepared and characterized. Then, metabolic syndrome was provoked by 60% fructose diet in male Sprague Dawley rats where carnosine and carnosine-loaded niosomes were orally administered at doses 50 mg/kg and 25 mg/kg, respectively. In addition, biochemical and molecular studies were performed to clarify the possible mechanisms of action. Data showed that the consumption of 60% fructose diet displayed a tremendous increment in body weight, body mass index as well as a significant elevation in levels of serum glucose, insulin, TAG, TC, LDL-c, VLDL-c and FFA. Also, it showed a significant reduction in levels of serum HDL-c. Furthermore, HFD provoked up-regulation of SREBP-1c and FAS mRNA levels in adipose tissue. Also, it induced down-regulation of SIRT1, GLUT-4 mRNA levels in adipose tissue. We found that oral administration of either carnosine or carnosine-loaded niosome effectively reversed HFD-mediated alterations via SIRT1 activation. Overall, oral delivery of carnosine-loaded niosome had a better efficacy than oral carnosine, attenuating HFD-mediated alterations. Carnosine nano-formulation is a new excellent candidates for metabolic syndrome management and needs further exploration of its mechanisms.

Traditional processing techniques impacted the bioactivities of selected local consumed foods

Epidemiological and clinical studies have evidenced the crucial role of vegetables and mushrooms for our health. Vegetables and mushrooms are usually cooked before consumption which induces many physicochemical changes in foods. A change in the phytochemical content might alter the health benefits of the food. In this regard, the impact of domestic cooking particularly boiling, steaming and stir-frying at different time intervals (under-cooked, well-done and overcooking) on the phenolic content and antioxidant potential of locally grown Allium cepa L., Brassica chinensis L., Pleurotus sajor-caju and Moringa oleifera Lam leaves and pods were investigated. The anti-proliferative effects of the fresh and cooked vegetables were assessed on the hepatocellular carcinoma (HepG2) cell line. The results demonstrated a general increase in the phenolic content of A. cepa, P. sajor- caju, M. oleifera leaves and pods, but a decrease in B. chinensis after cooking. Both the raw and the cooked vegetables and mushroom demonstrated notable free radical scavenging abilities, potent ferric reducing antioxidant power and strong iron chelating activity across the different processing methods. Cooking significantly increased reducing potential of M. oleifera leaves and P. sajor-caju, while a significant decline was observed for B. chinensis and M. oleifera pods after thermal treatments. Boiling and stir-frying caused significant loss in the chelating potential of B. chinensis (p<0.05). In addition, cooking enhanced the anti-proliferative properties of B. chinensis, P. sajor-caju and M. oleifera leaves against liver cancer cells. The present data provide a new insight into the influence of conventional cooking methods on locally cultivated foods, highlighting the importance of choosing the appropriate processing technique to maximize bioaccessibility of the beneficial bioactive compounds.

Preparation of Tryptanthrin Derivates Bearing a Thiosemicarbazone Moiety to Inhibit SARS-CoV-2 Replication

SARS-CoV-2 is a serious viral pathogen, and agents that inhibit its replication are in high demand. In the present work, we prepared two novel tryptanthrin derivates bearing a thiosemicarbazone moiety as potential antiviral agents. Both compounds displayed potent chelation activity against Fe(III/II) ion-associated COVID-19. The molecular docking results suggest that the compounds can display significant affinity towards SARS-CoV-2 papain-like proteases and SARS-CoV-2 main proteases. In addition, administering T8H-TSC can repress viral replication in the used model (Vero cells). Moreover, the therapeutic potential of the prepared compounds was predicted and analysed in terms of Lipinski’s rules, drug-likeness and drug score.