Related Compounds Research Articles

Environmental exposure to melamine and its derivatives and kidney outcomes in children

Melamine caused acute nephrotoxicity in a past food adulteration incident, but it is unclear whether and how widespread ambient exposure to melamine and related compounds might affect pediatric kidney health. We assessed cross-sectional associations between childhood exposure to melamine and its derivatives and biomarkers of kidney injury and health and explored potential heterogeneity by sex suggested by sex-dependent differences in renal physiology. We measured melamine and its derivatives ammeline, ammelide, and cyanuric acid (CYA) in spot urine samples collected from 192 children from an urban site (Seattle, WA) and 187 children from a rural site (Yakima, WA) aged 4–8 years in the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) Study. In addition, biomarkers of kidney injury were measured in the same urine samples, including albumin, total protein, KIM-1, NAG, NGAL, and EGF. We utilized linear regressions to examine associations between individual chemical exposures and kidney biomarkers. Interaction terms examined association modification by sex, as well as potential interactions between melamine and CYA. Despite comparable exposures, girls had higher levels of many kidney injury biomarkers compared to boys. A ten-fold higher melamine concentration was associated with a 18% (95% CI: 5.6%, 31%) higher EGF in the full sample, while ten-fold higher melamine was associated with a 76% (14.1%, 173%) higher KIM-1 in boys but not in girls (−10.1% (−40.6%, 36.1%), interaction p = 0.026). Melamine exhibited significant negative interactions with CYA in association with total protein and NAG that appeared to be specific to girls. Our results suggest possible associations between melamine exposure and markers of kidney injury that may be more pronounced in boys. These findings provide novel insights into melamine and related derivative compound health effects at low levels of exposure in children and emphasize the role of sex in mediating the relationship between nephrotoxicant exposure and kidney injury.

Synthesis, optical properties, and application of novel chalcone skeleton as pH fluorescent probe: Based AIE + ESIPT strategy

A series of “turn off” pH fluorescence probes with chalcone skeleton for basic system have been developed. The molecules emitted bright yellow fluorescence under acidic condition, resulting AIE coupled ESIPT characteristic and ICT process. What’s more, the compounds exhibited excellent sensitivity and selectivity for detecting pH as a facile “On-Off” fluorescence probe, and the fluorescence of them were quenched with the ESIPT process interrupted under alkaline condition. Theoretical calculation for the related compounds also performed to verify the electron effect on photophysical properties and confirm the rational speculation on the mechanism.

A Practical Method for the Synthesis of Mesoionic 1,3-Diaryltetrazolium Derivatives Bearing a para-Substituted Phenyl Group at the 1- or 3-Position from Anilines

AbstractA simple, economical, and safe method for the synthesis of mesoionic 1,3-diaryltetrazolium derivatives bearing a para-substituted phenyl group at the 1- or 3-position via thiosemicarbazides was established. Such compounds were directly obtained from the corresponding para-substituted anilines instead of aryl isothiocyanates and arylhydrazines. The newly synthesized mesoionic compounds were successfully converted into the corresponding nitrosotetrazolium salts, which were utilized as catalysts for oxidation of an aliphatic alcohol and analyzed by cyclic voltammetry to determine the correlation between the catalytic efficiencies and redox potentials. The proposed method can be widely applied and is valuable for investigating the substituent effects in mesoionic and related compounds.

Formulation and Evaluation of Lipid-based Nanoformulation of Itraconazole

The powdered form of itraconazole is white, flavorless, and stable, but it dissolves slowly in water. In comparison to palmitic acid, stearic acid has a stronger affinity (2.57), as shown by the partition coefficient test. UV-visible spectra analysis reveals critical compound insights. Fourier-transform infrared (FTIR) identifies significant peaks in itraconazole and related compounds. tween 80 is selected for solid lipid nanoparticles (SLN) based on their appearance. Optimization using 0.5% w/v tween 80 yielded better particle capture. Thermal analyses display distinctive characteristics of itraconazole, palmitic acid, and polyvinyl alcohol. Viscosity studies mirror tear film behavior. Transmission electron microscope (TEM) images demonstrate SLN’s potential ocular application without irritation. Antifungal studies exhibit effective inhibition of Candida albicans and Aspergillus flavus growth. SN-7 reveals strong encapsulation efficiency, mean vesicle size, and sustained drug release over 12 hours. Pharmacokinetic studies shed light on SLNs’ influence on drug absorption and distribution, indicative of potential in drug delivery systems. These findings offer promising prospects in formulating enhanced drug delivery mechanisms and understanding their impact on drug pharmacokinetics. High-performance liquid chromatography (HPLC) analysis confirmed SN-7’s singular peak at 6.59 minutes. Both formulations showcased skin penetration and stability over three months under varied conditions. Skin irritation tests on rats indicated minimal reactions, affirming low irritancy, which is crucial for patient comfort and acceptance in topical drug delivery. These assessments ensure safety and effectiveness in treating fungal infections.

Organic nanoparticles based on aza-boron dipyrromethene derivatives for combined photothermal and photodynamic cancer therapy

Cancer is one of the major diseases that threaten human being's health and life. Recently, phototherapy has gained great attention due to the advantages of high selectivity and low toxicity. Nonetheless, the development a single photosensitizer capable of simultaneously achieving photothermal and photodynamic effects remains a great challenge. Aza-boron-dipyrromethene (aza-BODIPY) dyes have been widely studied in biomedical area for their significant absorption in the near infrared region and high fluorescence quantum yield. In this contribution, three aza-BODIPY molecules (TAS-BP, TES-BP and TESO-BP) that conjugated with triphenylamine (TPA) or tetraphenylethylene (TPE) were designed and synthesized. The presence of donor-acceptor-donor pairs within compounds enables the intermolecular electron transfer, leading to the augmentation of near-infrared (NIR) absorbance and the generation of non-radiative heat. The nanoparticles were prepared via the assembly of the related organic compounds with amphiphilic polymer (DSPE-PEG2000), which were named as TAS-BP NPs, TES-BP NPs and TESO-BP NPs, respectively. Importantly, three nanoparticles can generate heat and reactive oxygen species (ROS) simultaneously induced by a single laser (808 nm). The photothermal conversion efficiency of TAS-BP NPs, TES-BP NPs and TESO-BP NPs were determined to be 64.5%, 65.7%, and 53.6%, respectively. Furthermore, the cellular experiments demonstrated the good biocompatibility and outstanding photocytotoxicity of three nanoparticles, and the TES-BP NPs exhibited the highest photodynamic/photothermal synergistic effect. Thus, the as-prepared organic nanomaterials were demonstrated as potential candidates for cancer treatment through phototherapy.

Abstract 1812: Development of novel topoisomerase 1 inhibitor PBX-7 payload-based ADC including tandem cleavable linker system

Abstract Antibody-Drug Conjugates (ADC) employing camptothecin-based payloads are gaining high interests as a new modality to treat various cancers, especially solid tumors. Among them, novel ADCs containing synthetic camptothecin-based payloads specially optimized for ADC applications (e.g., DXd) are of special interest due to their successful clinical results. Despite the remarkable success of ADCs exploiting these payloads, such as Enhertu (DS-8201a), there are still clear unmet needs, including the improvement of safety profile (minimization of ILD and neutropenia) and the development of novel ADCs with multiple MoA payloads to combat cancer heterogeneity. To address these unmet needs, we have synthesized and evaluated a series of PBX-7 payloads, derived from novel camptothecin FL118, a potent, dual inhibitor of Top 1/anti-apoptotic pathway known for its favorable safety profile. These compounds showed strong in vitro cytotoxicity across various cancer cell lines and inhibition of Top 1 comparable to DXd or other related camptothecin compounds. They had excellent safety profile in the preliminary toxicity study in mice that can be attributed to their physicochemical properties. PBX-7 series payloads based ADC exhibited superior cellular cytotoxicity and in vivo tumor regression compared to Enhertu in Her2-positive cell line and CDX mouse model. Notably, PBX-7 based ADC demonstrated remarkable efficacy in reducing tumor volume more than Enhertu in the T-DM1-resistant JIMT-1 xenograft mouse model. Furthermore, PBX-7 based ADC have bystander effects similar to Enhertu, leading to reduced viability of antigen-negative cells when co-cultured with antigen-positive cell lines. In NHP toxicity study in Cynomolgus monkeys, no sign of toxicity was observed when dosed with Trastuzumab-PBX-7016 up to 30mg/kg. As another way of addressing unmet needs, we synthesized novel linker including tandem cleavage site to reduce payload mediated toxicity. Two distinct enzyme, beta-glucuronidase and cathepsin B cleave linker sequentially. This linker system has a higher stability during circulation in the body and higher specific payload release in the tumor tissue than single cleavable linker. In conclusion, our research shows the promising potential of novel camptothecin PBX-7 based ADCs and tandem cleavable linker system as potent and safe ADC candidates for cancer therapy. These advancements hold great promise in addressing the current challenges in ADC development with their enhanced safety profiles and targeted efficacy. Citation Format: Younghwa Chun, Areum Go, Hyun Yong Cho, Byeong Sung Lee, Seunggun Shin, JaeHyeon Lee, Sohui Kweon, Hyemin Han, Suhyun Park, Doo Young Jung. Development of novel topoisomerase 1 inhibitor PBX-7 payload-based ADC including tandem cleavable linker system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1812.

Synthesis and biological activity of thiophene bioisosteres of natural styryl lactone goniofufurone and related compounds

Ten new thiophene derivatives related to goniofufurone have been obtained by multistep synthesis starting from d-glucose. The critical step of the synthesis was the Grignard reaction of 2-thienyl magnesium bromide with a protected dialdose, yielding the C-5 epimeric thiophene derivatives 9 and 10. The mixture was oxidized to the 5-keto derivative 11, which after deprotection was converted to the corresponding keto-lactone 14. Stereoselective reduction of 14 afforded the thiophene mimic of goniofufurone 3. Esterification of 3 with cinnamic or 4-fluorocinnamic acid gave hybrids 5–7. Synthesized analogues were evaluated for their in vitro cytotoxicity against several tumour cell lines. The vast majority of them showed better activity than lead 1. In the culture of K562 cells, compound 3 was more active than the commercial antitumour drug doxorubicin. Structural features of analogues important for their antiproliferative activities were identified by SAR analysis. Pro-apoptotic potential examination of compound 3 on the K562 cell line was performed using flow cytometry, double fluorescence staining and apoptotic morphology screening. Results show that this derivative induces cell membrane disruptions attributable to apoptosis and induces the apoptotic morphology, but decreasing simultaneously the population of cells in the subG1 phase of the cell cycle. The results further suggest that analogue 3 achieves strong cytotoxicity without causing DNA fragmentation. This is clearly indicated by the relatively low incidence of micronuclei, as well as the SAR analysis of all biological effects.

Nitrogen-doped carbon supported iron nanoparticles for mild catalytic hydrocracking of Xilinguole lignite

Cleaving C-O bridged bonds of lignite via catalytic hydrocracking (CHC) is an effective method to produce chemicals and clean fuels. Herein, a nitrogen-doped carbon supported Fe catalyst was developed by using a one-pot method for CHC of Xilinguole lignite (XL) and its related model compounds. The doped nitrogen enhanced the interaction between Fe and N species to form Fe-N sites and favored forming smaller Fe/Fe3C nanocrystals, which played a crucial role in CHC performance. Toluene and phenol were produced from CHC of benzyl phenyl ether (BPE) with high yield and selectivity at 250 °C over the optimal catalyst with 4% Fe, without hydrogenation products. The Fe-based catalyst activated both H2 and isopropanol to generate hydrogen radicals for cleaving C-O bridged bonds. The CHC of XL under different temperature and time showed that the yields of oil, asphaltene and preasphaltene were obviously promoted under 325 °C, 1 MPa, and 6 h, and they had much higher H/C ratio but remarkably lower O/C ratio, resulting in much higher heating values (28.19–36.90 MJ/kg) than XL. Phenols were the major group component with relative content of 53.6 wt% in oil from CHC, and the asphaltene and preasphaltene from CHC had obviously lower molecular weights, which could attributed to depolymerization of C-O bridged bonds in the XL macromolecular structures over the catalyst.

Lithium corrosion resistance of aluminum nitride prepared by structural doping with various elements

Influences of various doping elements on the corrosion behavior and possible failure mechanism of aluminum nitride ceramic in lithium had been investigated using X-ray diffraction and scanning electron microscope techniques. The results showed that different doping element could produce obvious effects on the corrosion behavior of aluminum nitride. In comparison with yttrium doping, better corrosion resistance in lithium could be achieved in zirconia doped aluminum nitride. This was attributed to a certain degree of compatibility of both the doped zirconium and its related compounds with lithium. Based on these observations, a corrosion resistance mechanism model was proposed, in which lithium was supposed to be hindered from diffusing into aluminum nitride by a network structure with the impurities, ie. ZrN and Al2.85N0.5O3.5, as the nodes. The corrosion resistance could also be improved effectively by fine and homogeneous grains due to the influences of grain sizes on the node number in network structure. Further studies on the corrosion behavior in embedded liquid lithium implied that the severity of corrosion had close relations with the sample surface quality.

Phytohormone and energy metabolism of rice germination and coleoptile growth during submergence by RNA-seq and LC-MS/MS analysis

Rice is one of the main food crops to guarantee the world's food security. Although rice is a semi-aquatic crop, long-term flooding stress can also inhibit growth and reduce yield and quality. Especially during the germination period, the germination rate of rice was inhibited by flooding stress, which resulted in the low emergence rate. Therefore, in this study, rice lines or cultivars with flood tolerance (C11) and flood sensitivity (KY60) were screened, and analyzed the response mechanisms during seed germination at different time points of waterlogging stress through transcriptome and metabolome sequencing. Compared with C11, waterlogging stress significantly inhibited the germination and coleoptile growth of KY60. Certain pathways, including plant hormones, energy metabolism, and carbohydrate metabolism, were identified as significantly involved in the flooding stress response in rice. The plant hormone-related DEGs (IAA, SAUR, ARF, LOX) and metabolites (IAA, JA, GA, and SA) were identified to up-regulate gene expression levels and significantly up-accumulate phytohormone content in C11 to resist waterlogging stress. However, the ABA signaling pathway-related genes (ZHD, PLY) and ABA content were decreased in C11 under submerged conditions. It is beneficial for C11 to promote seed germination and coleoptile elongation under flooding conditions. A total of 150 DEGs (AMY, PGLR) and 58 related compounds were identified as involved in the energy metabolism and carbohydrate metabolism of rice after flooding stress. Candidate key genes and metabolite compounds were identified by combined RNA-Seq and LC-MS/MS correlation network analysis. This study provided insights to explore the flood-tolerance mechanism of rice and laid the foundation for the cultivation of new varieties of flood-tolerance rice.

Larvicidal activity of Acacia nilotica extracts against Culex pipiens and their suggested mode of action by molecular simulation docking

Mosquitoes are one of the deadliest and most hazardous animals on Earth, where they transmit several diseases that kill millions of people annually. There is an ongoing search almost everywhere in the world for more effective and contemporary ways to control mosquitoes other than pesticides. Phytochemicals are affordable, biodegradable biological agents that specialize in eliminating pests that represent a risk to public health. The effectiveness of Acacia nilotica methanol and aqueous leaf extracts against 4th instar larvae was evaluated. The results revealed that the methanol extract of A. nilotica had a noticeable influence on the mortality rate of mosquito larvae, especially at high concentrations. Not only did the mortality rate rise significantly, but the hatching of the mosquito eggs was potentially suppressed.Terpenes, fatty acids, esters, glycosides, pyrrolidine alkane, piperazine, and phenols were the most prevalent components in the methanol extract, while the aqueous extract of A. nilotica exclusively showed the presence of fatty acids. The insecticidal susceptibility tests of both aqueous and alcoholic extract of A. nilotica confirmed that the Acacia plant could serves as a secure and efficient substitute for chemical pesticides because of its promising effect on killing larvae and egg hatching delaying addition to their safety as one of the natural pesticides. Molecular docking study was performed using one of the crucial and life-controlling protein targets, fatty acid binding protein (FABP) and the most active ingredients as testing ligands to describe their binding ability. Most of the structurally related compounds to the co-crystallized ligand, OLA, like hexadecanoic acid furnished high binding affinity to the target protein with very strong and stable intermolecular hydrogen bonding and this is quite similar to OLA itself. Some other structural non-related compounds revealed extraordinarily strong binding abilities like Methoxy phenyl piperazine. Most of the binding reactivities of the majortested structures are due to high structure similarity between the positive control, OLA, and tested compounds. Such structure similarity reinforced with the binding abilities of some detected compounds in the A. nilotica extract could present a reasonable interpretation for its insecticidal activity via deactivating the FABP protein. The FABP4 enzyme inhibition activity was assessed for of both methanolic and aqueous of acacia plant extract and the inhibition results of methanol extract depicted noticeable potency if compared to orlistat, with half-maximal inhibitory concentration (IC50) of 0.681, and 0.535 µg/ml, respectively.

Efficient production of R-2-(4-hydroxyphenoxy) propionic acid by Beauveria bassiana using biofilm-based two-stage fermentation

In this work, a novel biofilm-based fermentation of Beauveria bassiana was employed to convert R-2- phenoxypropionic acid (R-PPA) to R-2-(4-hydroxyphenoxy) propionic acid (R-HPPA). The biofilm culture model of Beauveria bassiana produced a significantly higher R-HPPA titer than the traditional submerged fermentation method. Mannitol dosage, tryptone dosage, and initial pH were the factors that played a significant role in biofilm formation and R-HPPA synthesis. Under the optimal conditions, the maximum R-HPPA titer and productivity approached 22.2 g/L and 3.2 g/(L·d), respectively. A two-stage bioreactor combining agitation and static incubation was developed to further increase R-HPPA production. The process was optimized to achieve 100 % conversion of R-PPA, with a maximum R-HPPA titer of 50 g/L and productivity of 3.8 g/(L·d). This newly developed biofilm-based two-stage fermentation process provides a promising strategy for the industrial production of R-HPPA and related hydroxylated aromatic compounds.

2-Azidobenzaldehyde-Based [4+2] Annulation for the Synthesis of Quinoline Derivatives.

Quinoline is a privileged heterocyclic ring which can be found in many drug molecules and bioactive compounds. The development of synthetic methods for making quinoline derivatives continuously attracts the interest of organic and medicinal chemists. This paper highlights 2-azidobenzaldehyde-based [4+2] annulation for the synthesis of quinoline derivatives including fused and spiro-quinolines, quinoline-4-ols, 4-aminoquinolines, and related compounds.

Rice-Magnaporthe oryzae interactions in resistant and susceptible rice cultivars under panicle blast infection based on defense-related enzyme activities and metabolomics.

Rice blast, caused by rice blast fungus (Magnaporthe oryzae), is a global threat to food security, with up to 50% yield losses. Panicle blast is a severe form of rice blast, and disease responses vary between cultivars with different genotypes. Reactive oxygen species (ROS)-mediated signaling reactions and the phenylpropanoid pathway are important defense mechanisms involved in recognizing and resisting against fungal infection. To understand rice-M. oryzae interactions in resistant and susceptible cultivars, we determined dynamic changes in the activities of five defense-related enzymes in resistant cultivar jingsui 18 and susceptible cultivar jinyuan 899 infected with M. oryzae from 4 to 25 days after infection. We then performed untargeted metabolomics analyses to profile the metabolomes of the cultivars under infected and non-infected conditions. Dynamic changes in the activities of five defense-related enzymes were closely related to panicle blast resistance in rice. Metabolome data analysis identified 634 differentially accumulated metabolites (DAMs) between resistant and susceptible cultivars following infection, potentially explaining differences in disease response between varieties. The most enriched DAMs were associated with lipids and lipid-like molecules, phenylpropanoids and polyketides, organoheterocyclic compounds, organic acids and derivatives, and lignans, neolignans, and related compounds. Multiple metabolic pathways are involved in resistance to panicle blast in rice, including biosynthesis of other secondary metabolites, amino acid metabolism, lipid metabolism, phenylpropanoid biosynthesis, arachidonic acid metabolism, arginine biosynthesis, tyrosine metabolism, tryptophan metabolism, tyrosine and tryptophan biosynthesis, lysine biosynthesis, and oxidative phosphorylation.

EXPLORATION OF THE ACTIVE COMPOUNDS OF MORINGA OLEIFERA LAM AS HIV-1 REVERSE TRANSCRIPTASE INHIBITOR: A NETWORK PHARMACOLOGY AND MOLECULAR DOCKING APPROACH

Objective: This study aims to predict the active compound of Moringa oleifera for the treatment of Human Immunodeficiency Virus (HIV), specifically targeting the HIV-1 reverse transcriptase (HIV-1 RT) enzyme using network pharmacology and molecular docking approach. Methods: The active ingredients of M. oleifera, were screened from the Knapsack database. Subsequently, HIV-1 RT and its related target compounds were retrieved from the Genecard database. The analysis of common targets involved protein-protein interactions (PPI) analysis using string databases and constructing interaction IDs using Cytoscape software. Gene Ontology (GO) functional and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Molecular docking studies were conducted using AutoDock Vina software to validate the results of the network pharmacological analysis. Results: A total of 63 active ingredients and 8601 targets related to HIV-1 RT were identified. The network analysis, encompassing GO and KEGG enrichment, revealed strong associations of common targets with key signaling pathways such as Tumor Necrosis Factor (TNF), Toll Like Receptor (TLR), and apoptosis. Additionally, 11 compounds of M. oleifera including apigenin, benzyl isothiocyanate, benzylamine, caffeic acid, ferulic acid, epicatechin, kaempferol, gallic acid, luteolin, syringic acid and vanillin were identified as potential vital compounds. Molecular docking analysis highlighted apigenin and kaempferol as the most promising compounds, exhibiting the lowest binding affinity to the HIV-1 RT enzyme. These compounds correlated with caspase-3(CASP3), caspase-9 (CASP9), and BCL2 Apoptosis Regulator (BAX) protein, stimulating cell apoptosis through multiple pathways. Conclusion: The study highlighted that apigenin and kaempferol are potential compound of M. oleifera in HIV-1 treatment through inhibition activity at HIV-1 RT Enzyme.

DFT study of the spectroscopic behaviour of different iron(II)-terpyridine derivatives with application in DSSCs

Through a comprehensive computational analysis utilizing Density Functional Theory (DFT), we clarify the electronic structure and spectroscopic properties of modified iron(II)-terpyridine derivatives, with the aim of enhancing the efficiency of Dye-Sensitized Solar Cells (DSSCs). We optimized a series of nineteen iron(II)-terpyridine derivatives and related compounds in acetonitrile (MeCN) as the solvent using TDDFT, evaluating their potential as dyes for DSSCs. From the conducted computations on the optimized geometries of the nineteen [Fe(Ln)2]2+ complexes, containing substituted terpyridine and related ligands L1-L19, we determined the wavelengths (λ in nm), transition energy (E in eV), oscillator strength (f), type of transitions, excited state lifetime (τ), light harvesting efficiency (LHE), frontier orbital character and their energies (ELUMO/EHOMO), natural transition orbitals (NTOs), injection driving force of a dye (ΔGinject), and regeneration driving force of a dye (ΔGregenerate). Results show that the theoretically calculated values for assessing dye efficiency in a DSSC correlate with available experimental values. The UV–visible spectra of [Fe(Ln)2]2+ exhibited a peak above 500 nm (λmax) in the visible region, attributed to the ligand-to-metal charge transfer band (LMCT) in literature, and a significant absorbance peak at approximately 300 nm (λA,max) in the UV region. The M06-D3/CEP-121G method replicated all reported λmax and λA,max values with a mean absolute deviation (MAD) of 21 and 18 nm, respectively. Our findings underscore the connections between electronic modifications and absorption spectra, emphasizing their impact on the light-harvesting capabilities and overall performance of DSSCs. This research contributes to the advancement of fundamental principles governing the design and optimization of novel photovoltaic materials, facilitating the development of more efficient and sustainable solar energy technologies.

Development of a targeted and non-targeted direct-injection analysis of plastic-related contaminants in liquor products

Alcoholic beverages and liquor products are susceptible to contamination throughout the production process by potentially harmful substances, among which plastic related compounds are of particular concern due to the lack of knowledge regarding their occurrence and effects on human health. The present study aimed to survey several liquor products collected in Canada for the presence of common bisphenols, phthalates, and other plastic related compounds, and to develop and apply a direct-injection non-targeted HPLC-QToF MS method for investigating suspected and unanticipated chemical constituents in a variety of high-proof alcohol products in various types of packaging. Overall, the targeted analysis detected no bisphenols in any of the liquor products (n = 37), while DEHP and DEHA were frequently detected, at levels up to nearly 300 and 95 ng/mL, respectively. For the first time, DPP was detected in vodka, BBzP detected brandy, and DEHA in vodka, rum, whiskey, whisky, gin, and brandy. The non-targeted workflow was validated for the targeted compound list and the identity of 3 additional compounds outside the original scope, liquiritigenin, ethylparaben, and ethylvanillin, was confirmed. Overall, the type of packaging type did not have a significant impact on the chemical contaminant profile of the liquors, however, the product type and production process seemed to play a role in the contaminant profile. The methodology developed provides for a fast and simple way of analyzing liquor products for purposes of contaminant surveillance, comparison, as well as for characterization. To our knowledge, this is the first report for applying LC-MS on the non-targeted analysis of plastic-related contaminants in high-proof alcoholic beverages.

Melatonin and Related Compounds as Antioxidants.

Oxidative stress has been reported to be involved in the onset and development of several diseases, including neurodegenerative and cardiovascular disorders, some types of cancer, and diabetes. Therefore, finding strategies to detoxify free radicals is an active area of research. One of these strategies is the use of natural or synthetic antioxidants. In this context, melatonin (MLT) has been proven to possess most of the required characteristics of an efficient antioxidant. In addition, its protection against oxidative stress continues after being metabolized, since its metabolites also exhibit antioxidant capacity. Based on the appealing properties of MLT and its metabolites, various synthetic analogues have been developed to obtain compounds with higher activity and lower side effects. This review addresses recent studies with MLT and related compounds as potential antioxidants.

Studies on Secondary Metabolites and In vitro and In silico Anticholinesterases Activities of the Sea Urchin Echinometra mathaei Crude Venoms from the Persian Gulf-Bushehr

Background: Echinoderms are a unique source of amazing secondary metabolites with a wide spectrum of biological activities. Several species of sea urchins contain various toxins and biologically active metabolites. One of the most attractive approaches to treat Alzheimer's disease is searching for effective marine natural products with cholinesterase inhibitory activities. Objective: The current study is designed to investigate the in vitro and in silico acetylcholinesterase and butyrylcholinesterase inhibitory activities of the Persian Gulf echinoderm sea urchin Echinometra mathaei venom and related chemical compounds. Methods: The experiments for LD50, total protein, protein bands, in vitro cholinesterase inhibitory activities, the identity of secondary metabolites, and the in silico evaluations, respectively, were performed by Spearman-Karber, Lowry, SDS-PAGE, Ellman's spectroscopic, GC-MS, and docking methods. Results: The LD50 (IV rat) of the spine, gonad, and coelomic fluid from sea urchin samples were 2.231 ± 0.09, 1.03 ± 0.05, and 1.12 ± 0.13 mg/ml, respectively. The SDS-PAGE and total protein studies showed that at least a portion of the venom is protein in nature. GC-MS analysis of the identified samples revealed 12, 23, and 21 compounds with different chemical types, including alkaloids, terpenes, and steroids, respectively. According to the results, all samples act as significant inhibitors of both enzymes. In silico data for the identified compounds also confirmed the experimental results. Conclusion: The alkaloid compound 6H-Indolo[3,2,1-de] [1,5] naphthyridine-6-one,1,2,3a,4,5- hexahydro-8-hydroxy-3-methyl (C7) had the highest affinity for both enzymes. Further research is needed to determine whether C7 could be a therapeutic candidate for Alzheimer's disease.

Pharmaceuticals in the Water: Emerging Concerns and Innovative Remediation Solutions

Abstract: Pharmaceutical contamination, resulting from the discharge of active pharmaceutical ingredients (APIs) and other related compounds into the water, has become a growing concern due to its potential adverse effects on ecosystems and human health. This review article aims to examine the many facets of pharmaceutical contamination and highlight the most recent developments in its remediation. The effects of pharmaceuticals, sources, and pathways of pharmaceutical contamination, as well as the difficulties in detecting and evaluating its toxicities, have been included in the present manuscript. Nowadays various remediation strategies are employed to mitigate pharmaceutical contamination in water. Conventional wastewater treatment techniques, including activated sludge processes and membrane filtration, are effective in removing a portion of the pharmaceutical compounds. However, advanced oxidation processes such as ozonation and photocatalysis have shown promising results in enhancing the degradation of recalcitrant APIs. Nanotechnology-based approaches, such as the use of nanoparticles for adsorption and degradation, and bioremediation methods utilizing microbial degradation, enzymatic processes, and phytoremediation, offer potential future directions for efficient and sustainable remediation. This review describes the most recent developments, current status, and potential research directions with the future prospects of pharmaceutical pollutants.