Chemico-Biological Interactions最新文献

{"title":"Ubiquitination: A non-negligible modulator in doxorubicin-induced cardiotoxicity","authors":"Can Gao ,&nbsp;Changxu Lu ,&nbsp;Jinwen Wei ,&nbsp;Zhongyi Mu ,&nbsp;Mingli Sun ,&nbsp;Dan Dong ,&nbsp;Zhenning Liu","doi":"10.1016/j.cbi.2025.111664","DOIUrl":"10.1016/j.cbi.2025.111664","url":null,"abstract":"<div><div>Doxorubicin (DOX), an effective chemotherapeutic drug, is used to alleviate the progression of cancers. However, the cardiotoxic side effects of DOX significantly limit its broader clinical application. Therefore, it is extremely urgent to find effective therapeutic strategies to mitigate doxorubicin-induced cardiotoxicity (DIC). Ubiquitination, a crucial post-translational modification (PTM), is regulated by various ubiquitinases and subsequently marks and modulates the function of proteins. Notably, Numerous studies have found that ubiquitination is closely related to the progression of DIC. However, a comprehensive review of this field remains unreported. Therefore, this review will mainly summarize the critical role of ubiquitination in DIC-associated pathological mechanisms and various potential interventions. Collectively, a comprehensive understanding of ubiquitination in the progression of DIC contributes to providing a crucial theoretical basis and exploring new avenues for the management of DIC.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"419 ","pages":"Article 111664"},"PeriodicalIF":4.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between exposure to phthalates and cardiovascular disease: A comprehensive study utilizing NHANES data from 2005 to 2018 and network toxicology","authors":"Wei Gong ,&nbsp;Hongyan Zhu ,&nbsp;Xinran Sun ,&nbsp;Jinxiu Zhang ,&nbsp;Meiyun Lin ,&nbsp;Peng Sun","doi":"10.1016/j.cbi.2025.111651","DOIUrl":"10.1016/j.cbi.2025.111651","url":null,"abstract":"<div><div>Phthalates are widely recognized endocrine-disrupting chemicals. This study investigates the association between phthalate exposure and cardiovascular disease (CVD), with a particular focus on elucidating the underlying molecular mechanisms. First, an epidemiological analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005–2018 to assess the relationship between phthalate metabolites and CVD. Generalized linear models (GLM) and weighted quantile sum (WQS) regression were employed to evaluate the impact of phthalate exposure. Among 12,127 participants, 1301 were diagnosed with CVD. The results showed a significant positive association between phthalate mixtures and CVD prevalence. GLM analysis identified MECPP, MEHHP, MEOHP, and MBzP as independent predictors of CVD (<em>P</em> &lt; 0.05). WQS regression further demonstrated that the phthalate metabolite mixture exposure index was associated with CVD (OR = 1.21, 95 % CI: 1.07–1.37, <em>P</em> = 0.002), highlighting MEOHP, MECPP, MBzP, and MnBP as key contributors. Subgroup analysis revealed that these associations were strongest among individuals aged ≥60 years, females, and during the 2013–2014 NHANES cycle. To further explore the potential molecular mechanisms, we conducted a network toxicology analysis. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape 3.9.1 to identify key molecular targets associated with phthalate-induced CVD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that phthalate-induced CVD is linked to neuroactive ligand-receptor interactions, GABAergic synapses, the PI3K-Akt and JAK-STAT signaling pathways, and calcium signaling. Among 29 identified CVD-related targets, seven core targets (GABRA3, GABRG2, GABRA5, GABRA2, BCL2, CCND2, and PIK3CA) were strongly implicated in phthalate-induced cardiovascular toxicity. Molecular docking analysis further confirmed strong binding affinities between phthalate metabolites and key targets, particularly GABRA5, PIK3CA, and BCL2. This study provided robust evidence linking phthalate exposure to CVD and suggests that phthalate-induced cardiovascular toxicity may involve neuroactive signaling, apoptosis, and inflammation-related mechanisms. These findings offered valuable insights for future research and potential therapeutic strategies in environmental health and CVD prevention.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"420 ","pages":"Article 111651"},"PeriodicalIF":4.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144628101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel anticancer inhibitors targeting the PI3K/Akt/mTOR signaling route and apoptosis inducers: A study on the apoptosis mechanism via the intrinsic mitochondrial-mediated pathway","authors":"Digambar Yevale ,&nbsp;Viralkumar Buha ,&nbsp;Deepkumar U. Sangani ,&nbsp;Nishith Teraiya ,&nbsp;Chetan B. Sangani ,&nbsp;Nishant Patel","doi":"10.1016/j.cbi.2025.111635","DOIUrl":"10.1016/j.cbi.2025.111635","url":null,"abstract":"<div><div>The PI3K/Akt/mTOR pathway is a key target for cancer due to its essential role in cell proliferation. This study developed quinoline compounds as a potent PI3Kδ/mTOR inhibitor and apoptosis inducer. The investigation found that <strong>6i</strong> had the highest cytotoxicity against Raji and HeLa cells, with IC_50s values of 0.18μM and 0.39μM, respectively. Further, <strong>6i</strong> demonstrated substantial selectivity against dual targets PI3Kδ (IC₅₀ = 0.034μM) and mTOR (IC₅₀ = 0.047 μM). The kinase assay discovered that <strong>6i</strong> had a greater selectivity for PI3Kδ/mTOR compared to PI3Ks (α, β, and γ). Molecular investigation revealed that <strong>6i</strong> significantly reduced phosphorylated p-PI3K, p-Akt and p-RPS6 levels in Western blot, confirming PI3K/Akt/mTOR as the pathway of action. In addition, compound <strong>6i</strong> stopped the cell cycle at the G0/G1 phase and raised total apoptosis by 16.26%. These findings were substantiated by morphological alterations in the AO/EB staining. Furthermore, <strong>6i</strong>-treated cells increased intracellular ROS levels and reduced mitochondrial membrane polarization in a dose-dependent manner, indicating that apoptosis was mediated by a mitochondrial route. In addition, higher levels of Bax, Bax/Bcl-2 ratio, and cytochrome c also corroborated the fact that apoptosis was mediated <em>via</em> mitochondrial pathway. Also, treatment of compound increased fraction of caspase-3, caspase-9, and PARP-1 (excluding caspase-8), indicating that apoptosis was mediated <em>via</em> the intrinsic route. Besides, <em>in silico</em> studies had validated the anticancer effects of inhibiting PI3Kδ/mTOR. Moreover, <strong>6i</strong> demonstrated a promising safety profile in hERG assay. Taken together, our finding suggest that <strong>6i</strong> may be a potential candidate for further in vivo investigation.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"419 ","pages":"Article 111635"},"PeriodicalIF":4.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144628100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinetic and structural evidence for specific DMSO interference with reversible binding of uncharged bis-oximes to hAChE and their reactivation kinetics of OP-hAChE","authors":"Dora Kolić ,&nbsp;Oksana Gerlits ,&nbsp;Megan Kucharski ,&nbsp;Lukas Gorecki ,&nbsp;Nichole Joiner ,&nbsp;Andrey Kovalevsky ,&nbsp;Zoran Radić","doi":"10.1016/j.cbi.2025.111649","DOIUrl":"10.1016/j.cbi.2025.111649","url":null,"abstract":"<div><div>The structural basis of inhibitory effect of organic solvent dimethyl sulfoxide (DMSO) on human acetylcholinesterase (EC 3.1.1.7; hAChE) was inferred from the effect of DMSO on kinetics of reversible inhibition of uncharged, heterocyclic bis-oximes to hAChE, from DMSO effect on rates of reactivation of inactive organophosphate (OP)-hAChE conjugates by bis-oximes and by X-ray structures of bis-oxime and DMSO binding to hAChE. The reversible inhibition constant of DMSO for hAChE in 0.1 M phosphate buffer pH 7.4 at 22 °C, was K_i= (0.32 ± 0.04) % (or 45 ± 5 mM). The K_i of the bis-oxime LG-703 for hAChE was 3.2-fold larger in 1 % DMSO, consistent with direct competition between LG-703 and DMSO. The X-ray structure of the LG-703∗hAChE complex (PDB ID: 6U3P) shows DMSO and LG-703 bound to individual hAChE monomers, LG-703 in the chain A and DMSO in the chain B. In the co-crystallization both small molecules were present at a similar excess over their corresponding K_i values for hAChE (7.8-fold for DMSO and 6.5-fold for LG-703) and formation of two different complexes (DMSO∗hAChE and LG-703∗hAChE), in the same crystal, appears consistent with inhibition kinetics. Furthermore, rates of reactivation of paraoxon-inhibited hAChE (POX-hAChE) and of VX-hAChE by LG-703 and by a novel heterocyclic bis-oxime LG-1922 were reduced 2 – 3-fold in DMSO, consistent with observation of the active-center-bound DMSO molecules in the newly solved structure of the LG-1922∗POX-hAChE complex presented here and in our POX-hAChE structure (PDB ID: 8DT2) showing obstruction of the reactivator access to the conjugated P atom.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"419 ","pages":"Article 111649"},"PeriodicalIF":4.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144628099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to chlorothalonil in zebrafish: modulation and biotransformation potential of two cytosolic GST isoforms","authors":"Juliano da Silva Barreto ,&nbsp;Viviane Barneche Fonseca ,&nbsp;Agatha Andriele Scheffel Viana ,&nbsp;Mackaullen Borges Gomes ,&nbsp;Juliana Zomer Sandrini ,&nbsp;Juliano Zanette ,&nbsp;Michael González-Durruthy ,&nbsp;Carlos Eduardo da Rosa","doi":"10.1016/j.cbi.2025.111652","DOIUrl":"10.1016/j.cbi.2025.111652","url":null,"abstract":"<div><div>Glutathione S-transferases (GSTs) are enzymes involved in the Phase II biotransformation of xenobiotics, including chlorothalonil (CLT), an organochlorine biocide used in agriculture, and antifouling paints. However, GSTs comprise a family of related enzymes and specific isoforms that are preferentially involved in CLT metabolism have not yet been identified. Thus, the objective of this study was to identify whether the two cytosolic GST isoforms expressed in zebrafish gills (GSTP and GSTA) were modulated by CLT exposure and their potential to participate in CLT metabolism in this species. Initially, the activity of both GST isoforms was evaluated in zebrafish gills after chlorothalonil exposure (to 0.1 and 10 μg/L) for 4 and 7 days. The highest CLT concentration tested (10 μg/L) significantly increased GSTP activity after 4 days of exposure and the activity of GSTA after 7 days of exposure. The mRNA levels of the gstp (gstp1 and gstp1) and gsta (gsta1 and gsta2) isoforms were also evaluated in fish gills after exposure to the same CLT concentration, but no significant alteration was observed. Finally, <em>in silico</em> analysis strongly suggests that CLT could interact with the active site of both GST isoforms with good binding affinity, following a spontaneous thermodynamic process (ΔG &lt; 0 kcal/mol). The approach employed here indicated that both GST isoforms could be involved in the biotransformation of CLT in the gills of D. rerio while protecting the fish against the deleterious effects of contaminants.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"419 ","pages":"Article 111652"},"PeriodicalIF":4.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standard in vitro co-culture conditions for studying inter-organ interactions between liver, breast cancer, and heart models","authors":"Gabriela Ulanowicz,&nbsp;Malgorzata Gluchowska,&nbsp;Agnieszka Zuchowska","doi":"10.1016/j.cbi.2025.111659","DOIUrl":"10.1016/j.cbi.2025.111659","url":null,"abstract":"<div><div>Interactions between organs are crucial for the proper functioning of the body and the maintaining of homeostasis, so their reflection in <em>in vitro</em> studies is necessary. These interactions occur, among other things, through secretory compounds secreted by cells that, after entering the bloodstream, affect other organs. Therefore, <em>in vitro</em> studies should not be limited to recreating single tissue models, such as in the form of three-dimensional structures for testing cancer therapies or disease modeling. In the present study, the focus was on reproducing organ-to-organ communication <em>in vitro</em> using three-dimensional cultures of liver, breast cancer and heart models. The goal was to investigate whether the metabolites produced by these models, released into the culture medium, affect the functioning of the other models. The applied approach made it possible to observe significant differences in the metabolic activity of cell aggregates, the level of glucose consumption and the expression of selected proteins.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"419 ","pages":"Article 111659"},"PeriodicalIF":4.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First toxicity profile prediction for mesembrine – archetypal psychoactive Sceletium alkaloid: prediction of key toxicological endpoints important to clinical and forensic toxicology using a multi-faceted in silico approach","authors":"Łukasz Niżnik ,&nbsp;Kamil Jurowski","doi":"10.1016/j.cbi.2025.111648","DOIUrl":"10.1016/j.cbi.2025.111648","url":null,"abstract":"<div><div>This study aims to perform a comprehensive <em>in silico</em> toxicological assessment of mesembrine using multiple computational tools to evaluate its safety profile, with relevance for both clinical and forensic toxicology. A canonical SMILES representation of mesembrine was analyzed using a suite of qualitative and quantitative prediction platforms: ADMETlab 3.0, admetSAR 3.0, Deep-PK, ProTox 3.0, STopTox, TEST 5.1.2, ACD/Percepta, and VEGA QSAR 1.2.3. These tools were used to predict acute toxicity (LD₅₀), organ-specific toxicity, genotoxicity, cardiotoxicity (hERG inhibition), and skin/eye irritation. Mesembrine was predicted to have moderate acute toxicity, with estimated oral LD₅₀ values in rats ranging between 340 and 370 mg/kg, corresponding to GHS Category 4. Organ-specific toxicity models indicated a high probability of adverse effects on the respiratory and renal systems, with conflicting predictions for hepatotoxicity. A low-to-moderate probability of hERG channel inhibition suggests potential cardiotoxicity at elevated concentrations. Genotoxicity (Ames test) predictions consistently placed mesembrine in the non-mutagenic category. However, predictions for dermal and ocular irritation were inconclusive, with results varying between platforms. This study presents the first integrative <em>in silico</em> toxicological profile of mesembrine. While it supports a moderate toxicity classification, the results highlight specific concerns regarding respiratory, renal, and potential cardiac toxicity. Given the compound's psychoactive properties and growing commercial availability, further <em>in vitro</em> and <em>in vivo</em> studies are essential for comprehensive risk assessment and regulatory guidance, particularly in forensic toxicology contexts.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"419 ","pages":"Article 111648"},"PeriodicalIF":4.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-cancer analysis of acetylcholinesterase (AChE) expression by a data-driven approach: future directions of AChE in cancer neuroscience","authors":"Jiahui An ,&nbsp;Heidi Qunhui Xie ,&nbsp;Zhen Yan ,&nbsp;Xin Chen ,&nbsp;Ruihong Zhu ,&nbsp;Guanglei Yang ,&nbsp;Li Xu ,&nbsp;Zrinka Kovarik ,&nbsp;Karl Wah Keung Tsim","doi":"10.1016/j.cbi.2025.111647","DOIUrl":"10.1016/j.cbi.2025.111647","url":null,"abstract":"<div><div>There is evidence that the expression of acetylcholinesterase (AChE) is associated with the development of certain cancers. However, there are still insufficient studies to reveal the correlation between AChE expression and cancer development and prognosis from the perspective of pan-cancer. In this study, a comprehensive bioinformatics analysis of the pan-cancer expression signature of AChE was conducted through a data-driven approach. Pan-cancer datasets were obtained through online databases, including the Cancer Genome Atlas and Genotypic Tissue Expression databases. The correlation between <em>ACHE</em> expression and cancer prognosis was predicted by survival analysis. The results showed differences in the expression levels of the <em>ACHE</em> gene in cancer and paired normal tissues. However, the alterations in cancer tissue <em>ACHE</em> expression were different depending on the cancer type, e.g., higher <em>ACHE</em> expression was found in pancreatic adenocarcinoma, and lower <em>ACHE</em> expression was found in glioblastoma multiforme (GBM). In addition, <em>ACHE</em> expression was found to have dual prognostic significance, e.g., cutaneous melanoma with higher levels of <em>ACHE</em> expression had better overall survival, while the opposite outcome was found in uveal melanoma. The function of <em>ACHE</em>-expressing cells in primary and metastatic tumors was predicted using single-cell RNA sequencing datasets from patients with GBM. Differences in cell type preferences for <em>ACHE</em> expression were found in primary and metastatic GBM, and different functional enrichment features were identified, suggesting a potential role of <em>ACHE</em> expression in GBM progression. Overall, our study highlights the potential of AChE as a target for cancer research.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"419 ","pages":"Article 111647"},"PeriodicalIF":4.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of gallates on 5α-reductase type 1: structure-activity relationship and implications for neurosteroid balance in neuropsychiatric disorders","authors":"Putian Zhang ,&nbsp;Wanyu Li ,&nbsp;Xinmiao Lu ,&nbsp;Shufang Qi ,&nbsp;Haonan Fang ,&nbsp;Junying Chen ,&nbsp;Baiping Mao ,&nbsp;Ren-shan Ge ,&nbsp;Yiyan Wang","doi":"10.1016/j.cbi.2025.111650","DOIUrl":"10.1016/j.cbi.2025.111650","url":null,"abstract":"<div><div>Neurosteroids modulate neural function, with their synthesis dependent on 5α-reductase type 1 (SRD5A1). Dysregulation of SRD5A1 has been implicated in neuropsychiatric disorders. Gallates, naturally occurring polyphenolic compounds, may modulate neurosteroidogenesis. This study aimed to evaluate the effects of gallic acid and eight gallate esters on human and rat SRD5A1 activity and characterize their structure-activity relationship. Using human SF126 glioblastoma cell microsomes and rat brain microsomes, we found inhibitory potency increased with carbon chain length from propyl (C3) to dodecyl (C12) gallate (IC₅₀ values: 168.29 to 20.53 μM), but diminished with cetyl (C16) gallate. Enzyme kinetic analyses revealed mixed/noncompetitive inhibition. Rat SRD5A1 showed reduced sensitivity to shorter-chain gallates compared to human SRD5A1. In intact cells, all active gallates significantly reduced dihydrotestosterone production. Molecular docking simulations showed gallates bind to the NADPH binding site, with binding energies correlating with inhibitory potency (−5.99 to −6.61 kcal/mol). The C16 chain of cetyl gallate extended beyond the optimal binding region, explaining its ineffectiveness at 100 μM. 3D-QSAR modeling identified hydrophobic features as critical for inhibition, while correlation analyses confirmed relationships between inhibitory potency and carbon length (C3–C12) and hydrophobicity properties. These findings provide structural insights for developing selective SRD5A1 modulators with potential applications in neuropsychiatric disorders.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"419 ","pages":"Article 111650"},"PeriodicalIF":4.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144613890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary prediction of toxicologically relevant physicochemical properties of Novichoks: the first comparative in silico studies","authors":"Maciej Noga ,&nbsp;Kamil Jurowski","doi":"10.1016/j.cbi.2025.111644","DOIUrl":"10.1016/j.cbi.2025.111644","url":null,"abstract":"<div><div>Advanced freely available and commercial <em>in silico</em> methods have been applied to predict the key physicochemical properties of Novichok agents, which are supertoxic organophosphorus compounds with limited experimental data due to their extreme toxicity and legal restrictions. Toxicologically relevant physicochemical properties including boiling and melting points, vapour pressure, water solubility, partition coefficients (log P, log K_OW, log K_OA), Henry's constants, and dissociation constants (pKa), were successfully predicted using appropriate <em>in silico</em> methods. These properties are essential for estimating, based on computational models, the toxicological characteristics, potential environmental behavior, and bioaccumulation tendencies of these hazardous substances. The validation process highlighted the strengths and limitations of the applied methods. OPERA and Percepta delivered the most accurate predictions for boiling and melting points, whereas the EPI Suite and TEST excelled in vapour pressure estimates. However, the significant variability in water solubility predictions underscores the need for methodological refinement and consensus approaches. Model predictions suggest that Novichok agents may exhibit high density (1–1.84 g/mL), moderate to high lipophilicity (logP: −0.68 - 3.06), and generally low vapour pressure (log VP: −6.09 - 10 mmHg). Despite these insights, all results should be interpreted as preliminary and hypothesis-generating, pending experimental validation. This study illustrates the potential utility, but also the current limitations, of <em>in silico</em> methods in the context of assessing supertoxic Novichok agents under conditions where experimental work is constrained.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"419 ","pages":"Article 111644"},"PeriodicalIF":4.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}