Structure-activity Relationship Research Articles

Combining in-situ quadrupole mass spectrometer analyses: Study on the structure–activity relationship and lubrication mechanisms of ammonium phosphate ionic liquids

Since the lubrication performances of ionic liquids are closely linked to their unique structures, four protic ionic liquids (PILs), [N44HH][DEHP], [N444H][DEHP], [N448H][DEHP] and [N4412H][DEHP], are designed to investigate the effect of cationic structures on the lubrication behaviors and lubrication mechanisms. Vacuum tribological tests were carried out to minimize the impact of the atmospheric environment. The structure–activity relationships and lubrication mechanisms of PILs were emphatically examined by in-situ quadrupole mass spectrometer (Q-MS) and XPS analyses. Results demonstrated that all four PILs exhibited outstanding lubrication performance under a vacuum condition. Unusually, extended alkyl chain cationic structures resulted in a changed lubrication mechanism, leading to a slight decrease in performance. In-situ Q-MS analyses and XPS further revealed that the length of the alkyl chain in cations influenced the strength of intermolecular forces in PILs, leading to changes in their lubrication performance and mechanisms.

Modulating structure of Ce-UiO-66 by introducing fluorinated terephthalic acid for enhanced removal efficiency of antibiotics: Insights into degradation kinetics and pathways

In this work, the 2-fluoroterephthalic acid with asymmetric structure and high electronegative F species was introduced in the assembly of Ce-UiO-66 catalysts to increase the defect density and enlarge pore structure for enhancement in removal efficiency of sulfamethoxazole. Owing to the strong coordination ability from high electronegative F species of 2-fluoroterephthalic acid with Ce-oxo nodes, the designed CUF exhibited improved interfacial properties (accelerated electron transfer rate, available active sites and enhanced interaction with PMS), which was favorable for the exploration and accessibility of active sites with sulfamethoxazole and PMS to decrease the adsorption barrier and accelerate PMS activation. As a result, the CUF catalysts exhibited higher adsorption capacity (173.4 mg/g) than that of CUH (117.8 mg/g), the enhanced degradation efficiency of sulfamethoxazole with a rate constant higher than 2.3 times CUH, good elimination (>95 %) of methylene blue, tetracycline and ibuprofen. In addition, the CUF/PMS system possessed satisfactory stability in wide solution pH, recycling and real water and good potential application in continuous wastewater treatment based on the designed dynamic catalytic reactor. This work provided deep insight into the design of catalysts with high adsorption performance and degradation efficiency based on the structure–activity relationship.

Quinoline-hydrazone Conjugates: Recent Insights into Synthetic Strategies, Structure-activity Relationship, and Biological Activities

: The fusion of two distinct and free pharmacologically active chemical moieties into single conjugate molecules can result in synergized pharmacological action of both moieties into the new composite molecule. Ultimately, it increases the therapeutic potentialof the newly formed hybrid compound which is more than the combination of each specific moiety’s therapeutic potential. So nowadays, it is common practice to combine at least two pharmacophores to create a particular compound with a powerful therapeutic effects. Quinoline has been reported with multiple pharmacological activities and industrial applications. On the other hand, hydrazones are also found very useful as herbicides, acaricides, rodenticides, insecticides, and various therapeutic applications. The conjugate containing quinoline and hydrazone is also being used as an anticancer, antibacterial, antifungal, antimalarial, anticonvulsant, anti-inflammatory, and antioxidant. The combination of two moieties yields a better therapeutic effect because of excellent efficacy and fewer side effects. Several synthetic methods have been employed in recent times to synthesize quinoline-hydrazone conjugates which are listed in the manuscript with their merits and demerits. The structure-activity relationship relating to their pharmacological actions with molecular structure has also been highlighted. The article aims to provide a good toolkit and comprehension to the medicinal chemists, for their future work, comprising of quinoline-hydrazone hybrid compounds.

Synthesis and Cytotoxic Activity of Quinazoline-benzofuran Conjugates.

In order to study on structure-activity relationships of benzofurans. Benzofuran is a kind of natural compound widely existing in nature with pharmacological effects. The development of new anticancer benzofuran derivatives has attracted more and more attention. We have introduced an active quinazoline unit into piperazine-substituted benzofuran, prepared a series of quinazoline-benzofuran compounds, and evaluated cytotoxic activity against a panel of human tumor cell lines by MTT assay. 48 novel quinazoline-substituted benzofuran derivatives have been prepared, and in vitro, cytotoxic activity against five human tumor cell lines was evaluated. The results indicated that some quinazoline-benzofuran conjugates showed selective inhibitory activity against tumor cell lines. We have found that compound 14x displayed excellent cytotoxic activity, which could be considered a potential anticancer agent.

Recent Advancements and SAR Studies of Synthetic Coumarins as MAO-B Inhibitors: An Updated Review.

The oxidative deamination of a wide range of endogenous and exogenous amines is catalyzed by a family of enzymes known as monoamine oxidases (MAOs), which are reliant on flavin-adenine dinucleotides. Numerous neurological conditions, such as Parkinson's disease (PD) and Alzheimer's disease (AD), are significantly correlated with changes in the amounts of biogenic amines in the brain caused by MAO. Hydrogen peroxide, reactive oxygen species, and ammonia, among other toxic consequences of this oxidative breakdown, can harm brain cells' mitochondria and cause oxidative damage. The prime objective of this review article was to highlight and conclude the recent advancements in structure-activity relationships of synthetic derivatives of coumarins for MAO-B inhibition, published in the last five years' research articles. The literature (between 2019 and 2023) was searched from platforms like Science Direct, Google Scholar, PubMed, etc. After going through the literature, we have found a number of coumarin derivatives being synthesized by researchers for the inhibition of MAO-B for the management of diseases associated with the enzyme such as Alzheimer's Disease and Parkinson's Disease. The effect of these coumarin derivatives on the enzyme depends on the substitutions associated with the structure. The structure-activity relationships of the synthetic coumarin derivatives that are popular nowadays have been described and summarized in the current study. The results revealed the updated review on SAR studies of synthetic coumarins as MAO-B inhibitors, specifically for Alzheimer's Disease and Parkinson's Disease. The patents reported on coumarin derivatives as MAO-B inhibitors were also highlighted. Recently, coumarins, a large class of chemicals with both natural and synthetic sources, have drawn a lot of attention because of the vast range of biological actions they have that are linked to neurological problems. Numerous studies have demonstrated that chemically produced and naturally occurring coumarin analogs both exhibited strong MAO-B inhibitory action. Coumarins bind to MAO-B reversibly thereby preventing the breakdown of neurotransmitters like dopamine leading to the inhibition of the enzyme A number of MAO-B blockers have been proven to be efficient therapies for treating neurological diseases like Alzheimer's Disease and Parkinson's Disease. To combat these illnesses, there is still an urgent need to find effective treatment compounds.

An automated computational data pipeline to rapidly acquire, score, and rank toxicological data for ecological hazard assessment.

Biological Evaluations support Endangered Species Act (ESA) consultation with the US Fish and Wildlife Service and National Marine Fisheries Service by federal action agencies, such as the USEPA, regarding impacts of federal activities on threatened or endangered species. However, they are often time-consuming and challenging to conduct. The identification of pollutant benchmarks or guidance to protect taxa for states and tribes when USEPA has not yet developed criteria recommendations is also of importance to ensure a streamlined approach to Clean Water Act program implementation. Due to substantial workloads, tight regulatory timelines, and the often-protracted length of ESA consultations, there is a need to streamline the development of biological evaluation toxicity assessments for determining the impact of chemical pollutants on ESA-listed species. Moreover, there is limited availability of species-specific toxicity data for many contaminants, further complicating the consultation process. New approach methodologies are being increasingly used in toxicology and chemical safety assessment to rapidly and cost-effectively provide data that can fill gaps in hazard and/or exposure characterization. Here, we present the development of an automated computational pipeline-RASRTox (Rapidly Acquire, Score, and Rank Toxicological data)-to rapidly extract and categorize ecological toxicity benchmark values from curated data sources (ECOTOX, ToxCast) and well-established quantitative structure-activity relationships (TEST, ECOSAR). As a proof of concept, points-of-departure (PODs) generated in RASRTox for 13 chemicals were compared against benchmark values derived using traditional methods-toxicity reference values (TRVs) and water quality criteria (WQC). The RASRTox PODs were generally within an order of magnitude of corresponding TRVs, though less concordant compared with WQC. The greatest utility of RASRTox, however, lies in its ability to quickly and systematically identify critical studies that may serve as a basis for screening value derivation by toxicologists as part of an ecological hazard assessment. As such, the strategy described in this case study can potentially be adapted for other risk assessment contexts and stakeholder needs. Integr Environ Assess Manag 2024;20:2203-2217. © 2024 Society of Environmental Toxicology & Chemistry (SETAC). This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Application of computer-aided drug design in drug discovery and development: Updating knowledge

Coronavirus (CoV) diseases are widespread throughout the world and have caused considerable socio-economic disruptions. For this reason, efforts have been made to develop a direct or indirect antiviral drugs against these diseases. However, no specific antiviral drug has yet been approved by the Food and Drug Administration (FDA) for CoV infections. Thus, the challenge in discovering therapeutic molecules against these infections remains pertinent. Computer-aided drug design (CADD) is one of the modern techniques for drug discovery and development. It accelerates the process, minimizes costs, and reduces research time. In this article, we present the three CADD approaches, namely structure-based drug discovery (SBDD), ligand-based drug discovery (LBDD) and high-throughput virtual screening (HTVS). The different methods used in these three approaches CADD, such as molecular modelling, target structure analysis, molecular docking, molecular dynamics simulation, pharmacophore modelling, quantitative structure-activity relationship (QSAR), ligand-based virtual screening (LBVS) and structure-based virtual screening (SBVS) are detailed. In addition, the bioinformatics tools and databases commonly used in these different CADD techniques are also described.

Dual COX-2/TNF-α Inhibitors as Promising Anti-inflammatory and Cancer Chemopreventive Agents: A Review

: Cyclooxygenases (COX) play a pivotal role in inflammation and are responsible for the production of prostaglandins (PGs). Two types of COXs have been identified as key biological targets for drug design: Constitutive COX-1 and inducible COX-2. Nonsteroidal anti-inflammatory drugs (NSAIDs) target COX-1, while selective COX-2 inhibitors are designed for COX-2. These COX isoforms are involved in multiple physiological and pathological pathways throughout the body. Overproduction of tumor necrosis factor-alpha (TNF-α) plays a role in COX-2's inflammatory activity. Tumor necrosis factor-alpha can contribute to cardiac fibrosis, heart failure, and various cancers by upregulating the COX-2/PGE2 axis. Therefore, suppressing COX activity has emerged as a potentially effective treatment for chronic inflammatory disorders and cancer. This review explores the mechanisms of TNF-α-induced COX-2/PGE2 expression, a significant pathophysiological feature of cancer development. Furthermore, we summarize chemical compounds with dual COX-2/TNF-α inhibitory actions, providing an overview of their structure-activity relationship. These insights may contribute to the development of new generations of dual-acting COX-2/TNF-α inhibitors with enhanced efficacy.

The Investigation of Hsp90C-Terminal Inhibitors Containing Amide Bioisosteres.

Heat Shock Protein 90 (Hsp90) is responsible for the proper folding and maturation of ~400 client protein substrates, many of which are directly associated with the ten hallmarks of cancer. Hsp90 is a great target for cancer therapy including melanoma, since Hsp90 inhibition can disrupt multiple oncogenic pathways simultaneously. In this study, we report the synthesis and anti-proliferative activity manifested by a series of Hsp90 C-terminal inhibitors against mutant BRAF and wild-type BRAF melanoma cells. Furthermore, we explored structure-activity relationships (SAR) for the amide moiety of 6 (B1), a novel Hsp90C-terminal inhibitor via introduction of amide bioisosteres. Compound 6 displayed an IC50 of 1.01 μM, 0.782 μM, 0.607 μM and 1.413 μM against SKMel173, SKMel103, SKMel19 and A375 cells, respectively.

Achievements and Challenges in Surfactants-Assisted Synthesis of MOFs-Derived Transition Metal-Nitrogen-Carbon as a Highly Efficient Electrocatalyst for ORR, OER, and HER.

Metal-organic frameworks (MOFs) are excellent precursors for preparing transition metal and nitrogen co-doped carbon catalysts, which have been widely utilized in the field of electrocatalysis since their initial development. However, the original MOFs derived catalysts have been greatly limited in their development and application due to their disadvantages such as metal atom aggregation, structural collapse, and narrow pore channels. Recently, surfactants-assisted MOFs derived catalysts have attracted much attention from researchers due to their advantages such as hierarchical porous structure, increased specific surface area, and many exposed active sites. This review mainly focuses on the synthesis methods of surfactants-assisted MOFs derived catalysts and comprehensively introduces the action of surfactants in MOFs derived materials and the structure-activity relationship between the catalysts and the oxygen reduction reaction, oxygen evolution reaction, and hydrogen evolution reaction performance. Apparently, the aims of this review not only introduce the status of surfactants-assisted MOFs derived catalysts in the field of electrocatalysis but also contribute to the rational design and synthesis of MOFs derived catalysts for fuel cells, metal-air cells, and electrolysis of water toward hydrogen production.

β-Carboline-3-carboxamide Antimalarials: Structure-Activity Relationship, ADME-Tox Studies, and Resistance Profiling.

The development of parasite resistance to both artemisinin derivatives and their partner drugs jeopardizes the effectiveness of the artemisinin combination therapy. Thus, the discovery of new antimalarial drugs, with new mechanisms of action, is urgently needed. We recently disclosed that β-carboline 1a was orally efficacious in Plasmodium berghei-infected mice and that it showed low cross-resistance between susceptible Plasmodium falciparum and four different drug-resistant strains. In this report, we describe the synthesis and in vitro antimalarial evaluation of 91 new derivatives of 1a. The asexual blood stage growth inhibition data show a clear preference for a 3,4-dihalogenated, 3,5-dihalogenated, 3,4,5-trichloro-, or 4-trifluoromethyphenyl ring at the C1-position. The most potent compound, 3,4,5-trichlorophenyl-substituted 42a, is twice as potent as 1a. Six potent analogues were assessed for their drug-like properties, and four of these were subjected to in vitro barcoded cross-resistance profiling. Compounds 1a, 1m, 42a, and 42m showed no cross-resistance to 32 resistance mutations on the Dd2 genetic background and 10 resistance mutations on the 3D7 genetic background. These data suggest that compounds in this scaffold possess a novel mechanism of antimalarial action.

Coordinatively Unsaturated Co Single-Atom Catalysts Enhance the Performance of Lithium-Sulfur Batteries by Triggering Strong d-p Orbital Hybridization.

The catalytic activities displayed by single-atom catalysts (SACs) depend on the coordination structure. SACs supported on carbon materials often adopt saturated coordination structures with uneven distributions because they require high-temperature conditions during synthesis. Herein, bisnitrogen-chelated Co SACs that are coordinatively unsaturated are prepared by integrating a Co complex into a conjugated microporous polymer (CMP-CoN2). Compared with saturated analogues, i.e., tetranitrogen-chelated Co SACs (denoted as CMP-CoN4), CMP-CoN2 exhibits higher electrocatalytic activity in polysulfide conversions due to an enhanced hybridization between the 3d orbitals of the Co atoms and the 3p orbitals of the S atoms in the polysulfide. As a result, sulfur cathodes prepared with CoN2 deliver outstanding performance metrics, including a high specific capacity (1393 mA h g-1 at 0.1 C), a superior rate capacity (673.2 mA h g-1 at 6 C), and a low capacity decay rate (of only 0.045% per cycle at 2 C over 1000 cycles). They also outperform sulfur cathodes that contain CMP-CoN4 or CMPs that are devoid of Co SACs. This work reveals how the catalytic activity displayed by SACs is affected by their coordination structures, and the rules that underpin the structure-activity relationship may be extended to designing electrocatalysts for use in other applications.

Flavonoid Based Development of Synthetic Drugs: Chemistry and Biological Activities.

The toxicity associated with synthetic drugs used for treating various diseases is common. This led to a growing interest in searching and incorporating natural functional core structures such as flavonoid and their derivativesviachemical modifications to overcome the toxicity problems andenhance their biological spectrum. Natural core structures such as flavonoids are accepted due to their safety to the environment and owing to their varieties of biological activities such as anti-Alzheimer, antimicrobial, anticancer, anti-inflammatory, antidiabetics, and antiviral properties.Based on their chemical structure, flavonoids are classified into various classes such as flavone, flavanol, flavanone, isoflavone, and Anthocyanin, etc.The present review focuses onthe potential role of the flavonoid ring-containing derivatives, highlighting their ability to prevent and treat non-communicable diseases such as diabetes, Alzheimer's, and cancer. The pharmacological activities of the flavonoid's derivatives are mainly attributed to their antioxidant effects against free radicals, and reactive oxygen species as well as their ability to act as enzymes inhibitors. The reviewcovers the synthetic strategies of flavonoid derivatives, structure activity relationship (SAR), andin silicostudies to improve the efficacy of these compounds. TheSAR,molecular docking analysis will enable medicinal chemists to search further, develop potent and newer therapeutic agents.

In Situ Self-Assembly of Antibody-Rhamnose Complex as a Pre-Targeting Strategy for Enhanced Cancer Immunotherapy.

Enhancing the Fc effector functions of monoclonal antibodies (mAbs) is a proven strategy for improving cancer immunotherapy. In this study, we present a novel pre-targeting approach that integrates host-guest chemistry with an antibody-recruiting concept to create mAbs with superior effector functions. Using rituximab (RTX), a clinically approved anti-CD20 mAb, as our model, we modified RTX by conjugating it with adamantane (Ada) derivatives and various polyethylene glycol (PEG) linkers to produce RTX-Ada conjugates. These conjugates effectively formed RTX-rhamnose (Rha) complexes in situ through self-assembly, driven by host-guest interactions with Rha-modified β-cyclodextrin. This mechanism successfully redirected endogenous anti-Rha antibodies to target cells, enhancing the availability of Fc domains for improved effector functions, including complement-dependent cytotoxicity (CDC). A structure-activity relationship study indicated that the potency of these in situ complexes was significantly influenced by the length of the PEG linker used; shorter PEG linkers correlated with higher CDC activity. Given the variability in endogenous antibody levels among individuals, this strategy presents a flexible and promising platform for enhancing the efficacy of mAb-based cancer immunotherapy.

Investigation of muscarinic acetylcholine receptor M3 activation in atomistic detail: a chemist's viewpoint.

We analyzed the precise ligand:receptor interactions required for activation of the muscarinic acetylcholine receptor M3, a prototypical G protein-coupled receptor and potential diabetes target. Starting from literature-known compounds and docking solutions, ligands were tailored for the modulation of this receptor's activation. Several aspects of the structure-activity relationship of agonists were investigated in atomistic detail, in order to delineate how the receptor can be activated via the orthosteric site. Such exquisitely precise knowledge is instrumental for designing potent and effiacious ligands. We put this strategy into practice and acquired or synthesized and measured a diverse set of 55 ligands ranging from small fragment-like amines coordinating D3.32 to bigger molecules extending towards helices 5 and 6 with diphenyl moieties. In the course of these investigations, we showed that the polarizability of the amine nitrogen and the rigidity and size of the moieties in the space delimited by helices 5 and 6 are the two key elements distinguishing potent and efficacious ligands from those that are not. The resulting data set will be highly useful in drug design and molecular machine learning alike.

Synthesis and Evaluation of Phenyltriazole-Deoxynojirimycin Hybrids as Potent α-Glucosidase Inhibitors

1-deoxynojirimycin (DNJ) is a well-known α-glucosidase inhibitor. A series of phenyltriazole-deoxynojirimycin hybrids containing C4 and C6 (4 and 6 methylenes, respectively) linkers were synthesized. These novel compounds were assessed for preliminary glucosidase inhibition and cytotoxicity tests in vitro. Among them, compounds 12–14 and 16–20 (IC50: 105 ± 9–11 ± 1 μM) were more active than deoxynojirimycin (DNJ, IC50 = 155 ± 15 μM). The kinetics of enzyme inhibition measured by using Lineweaver–Burk plots indicated that compounds 18 and 19 were competitive inhibitors. In addition, a molecular docking study of α-glucosidase revealed that the interaction modes and the orientations of compound 18 and DNJ were clearly different. Furthermore, in tissue culture, HL60 cell compounds showed no cytotoxicity at low concentrations. When the concentration reached 50 µM, only compound 20 exhibited cytotoxicity. The structure–activity relationships exhibit that the length of the linker and the nature of 4-position substituents on the phenyl have a significant effect on the inhibitory potency of glucosidases and cytotoxicity.

Strong Metal-Support Interactions in Heterogeneous Oxygen Electrocatalysis.

Molecular oxygen redox electrocatalysis involves oxygen reduction and evolution as core reactions in various energy conversion and environmental technology fields. Strong metal-support interactions (SMSIs) based nanomaterials are regarded as desirable and state-of-the-art heterogeneous electrocatalysts due to their exceptional physicochemical properties. Over the past decades, considerable advancements in theory and experiment have been achieved in related studies, especially in modulating the electronic structure and geometrical configuration of SMSIs to enable activity, selectivity, and stability. In this focuses on the concept of SMSI, explore their various manifestations and mechanisms of action, and summarizes recent advances in SMSIs for efficient energy conversion in oxygen redox electrocatalysis applications. Additionally, the correlation between the physicochemical properties of different metals and supports is systematically elucidated, and the potential mechanisms of the structure-activity relationships between SMSIs and catalytic performance are outlined through theoretical models. Finally, the obstacles confronting this burgeoning field are comprehensively concluded, targeted recommendations and coping strategies are proposed, and future research perspectives are outlined.

Novel Phenoxyalkanoic Acid Derivatives as Free Fatty Acid Receptor 4 Agonists for Treating Type 2 Diabetes Mellitus

Diabetes mellitus (DM) is a common metabolic disease that poses a severe threat to human health. Despite a range of therapeutic approaches, there remains a lack of effective and safe therapies with the existing drugs. Therefore, there is an urgent need to develop novel, effective, and safe therapeutic strategies for DM. Free fatty acid receptor 4 (FFAR4), also known as GPR120, is a member of the G protein-coupled receptor family, which has received considerable attention as an attractive new therapeutic target for treating DM. In the present study, based on the structure of TUG-891, which has excellent activity and selectivity, a series of novel FFAR4 agonists was designed by replacing the phenylpropanoic acid β position carbon atom with an oxygen atom, while replacing the linking oxymethylene with an amide-linking group. The target compounds were evaluated for FFAR4 agonistic activity, and the preferred compounds were evaluated for selectivity, oral glucose tolerance in normal ICR mice, antidiabetic activity in diet-induced obese (DIO) mice, pharmacokinetic properties in ICR mice and molecular modeling studies. The results showed that compound 10f possessed excellent FFAR4 agonistic activity and selectivity, significantly improved glucose tolerance in normal ICR mice, lowered blood glucose and promoted insulin secretion in a dose-dependent manner in DIO mice, and showed favorable pharmacokinetic properties. These results indicate that compound 10f may be a promising compound that deserves further structure–activity relationship and pharmacological studies for the development of antidiabetic drugs.

Biomarker and adverse outcome pathway responses of Tubifex tubifex(sludge worm) exposed to environmentally-relevant levels of acenaphthene: insights from behavioral, physiological, and chemical structure-activity analyses.

Polycyclic aromatic hydrocarbons (PAHs), including acenaphthene, pose a significant threat to aquatic ecosystems by harming vital organisms such as benthic invertebrates. This study evaluated the impact of environmentally relevant concentrations of acenaphthene on Tubifex tubifex, focusing on sublethal acute toxicity and subchronic biomarker responses. Key biomarkers assessed included histopathological changes and the modulation of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), and malondialdehyde (MDA). Additionally, the study examined structure-activity relationships and species sensitivity distribution (SSD). Concentrations exceeding the solubility threshold of acenaphthene (3.9 mg/L) triggered distinct, concentration-dependent behavioral responses in Tubifex tubifex, such as clumping, mucus secretion, and body wrinkling. Prolonged exposure exacerbated these behavioral dysfunctions, while subchronic exposure resulted in significant histopathological alterations, including epithelial hyperplasia, inflammation, edema, fibrosis, and degenerative changes. The edematic appearance of the body wall suggested a potential immune response to exposure. Furthermore, increased activities of CAT, SOD, and GST indicated oxidative stress in the worms. The study found a 1.5-fold increase in CAT and GST activity, a fivefold increase in SOD, and a striking 100-fold increase in MDA levels compared to controls, signifying an overwhelmed antioxidant defense system and potential cellular disruption. The SSD curve revealed hazard concentrations (HC50 and HC90), indicating that Tubifex tubifex exhibited lower sensitivity to acenaphthene compared to other taxa. In silico analysis and read-across models confirmed the potential of acenaphthene to induce significant oxidative stress upon exposure. The correlation between biomarker responses and structure-activity relationship analysis highlighted the aromatic nature of acenaphthene as a key factor in generating reactive metabolites, inhibiting antioxidant enzymes, and promoting redox cycling, ultimately contributing to adverse outcomes. These findings, coupled with behavioral responses and SSD curve inferences, underscore the importance of the solubility threshold of acenaphthene as a critical benchmark for evaluating its ecological impact in aquatic environments.

The Structure Characterization of Polysaccharides from Codonopsis pilosula and the Structure-activity Relationship with Immune-regulation on THP-1 Cells.

In recent years, polysaccharides from Codonopsis pilosula (CPs) have received increasing attention for their excellent behaviors in immune-regulation. However, the relationship between the structure and immunomodulatory activity has rarely been reported. In this work, four fractions purified from crude CPs (CPW, CPS0.2, CPS0.5, CPS1) by chromatographic column separation were explored with both structure and immunomodulatory effects by THP-1 cells. The results showed that the monosaccharide composition, chain conformation, molecular weight (Mw) and aggregated state of CPs were different. At the same time, the immunomodulatory effects of CPs were also varied depend on structure differences, as indicated by the released cytokines of TNF-α and IL-1β by LPS-induced THP-1 cells. Finally, we summarized and concluded that the spherical structure and smaller particle size of CPs were the key factors attributed to better immune-enhancing effects. The results showed that the monosaccharide combination differences of polysaccharides might lead to anti-inflammatory or pro-inflammatory activity. Moreover, the higher percentage of glucose, the relatively large particle size, as well as the extended chain conformation of CPs might be the key factors attributed to better immune-enhancing effects. This study aims to provide a theoretical basis for establishing the structure-activity relationship of CPs.