Chemico-biological interactions最新文献

{"title":"The synthesis and influence of the novel bispyridinium compound LB1 on the effectiveness of the standard antidotal treatment of organophosphorus nerve agent intoxicated mice and some structure-activity considerations.","authors":"Jiri Kassa, Rachael E Ambler, Lynda J Brown, Jaime Cummins, A Christopher Green, Christopher M Timperley","doi":"10.1016/j.cbi.2025.111470","DOIUrl":"https://doi.org/10.1016/j.cbi.2025.111470","url":null,"abstract":"<p><p>The design of MB327, a bispyridinium compound that ameliorates the nicotinic effects of acute organophosphorus nerve agent (NA) intoxication, followed an observation made by the German pharmacologist Klaus Schoene in the 1970s, who noted therapeutic activity in bispyridinium molecules missing the usual oxime group, CH=NOH. Some of these compounds protected mice against soman. One structurally related to obidoxime called HY10 had this action. Its oxime moieties were capped by tert-butyl groups: CH=NOtBu. We modified HY10 by changing the bridge between the pyridinium units from a dimethylene ether to a trimethylene group (CH₂OCH₂ → CH₂CH₂CH₂) and prepared a novel relative of trimedoxime, called LB1, whose synthesis and stereochemistry are described. Unlike obidoxime or trimedoxime, LB1, because of its capped oxime groups cannot directly reactivate NA inhibited acetylcholinesterase. Its antidotal activity in mice is now reported. The therapeutic efficacy of LB1, atropine alone, atropine with LB1, atropine with an oxime (HI-6, obidoxime or trimedoxime), and atropine with an oxime and LB1, was studied by determining the LD₅₀ values of the NAs soman, sarin, or tabun in mice treated with these compounds or mixtures. LB1 exceeded MB327 in toxicity and its activity was insufficient for a useful addition to the current standard antidotal treatment (protective ratio data are compared to those of MB327). Although this study produced largely negative biological results, the therapeutically beneficial mechanism of the effective bispyridinium non-oxime analogues is unclear, and has been demonstrated only in vivo. The present study points out directions in structural optimisation unlikely to yield the desired therapeutic outcomes and provides a literature review that could promote creative thinking for the design of widely-desirable non-oxime therapeutics for anticholinesterase inhibitors.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111470"},"PeriodicalIF":0.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Organ-on-Chip approach to study the impact of inter-organ communication on the efficacy and side effects of cancer therapy.","authors":"Paweł Romanczuk, Joanna Zajda, Magdalena Matczuk, Agnieszka Zuchowska","doi":"10.1016/j.cbi.2025.111460","DOIUrl":"https://doi.org/10.1016/j.cbi.2025.111460","url":null,"abstract":"<p><p>Cancer is one of the pathological conditions of the human body, which, due to its tissue diversity, is not fully understood. Currently used preclinical in vitro cell or animal models do not reflect the complexity and functional features of the human body, including its pathological conditions such as cancer. This fact is related to poor predictions of the effectiveness of newly developed drugs. Therefore, in our work, we focused on creating a tool that allows the reproduction of important morphological and biochemical features of the tumor in vivo, such as three-dimensional (3D) structure, heterogeneity, the presence of extracellular matrix (ECM), and the appropriate scale (volume to surface ratio). Moreover, the presented Multi-Organ-on-Chip (MOC) tool allows us to evaluate the effects of anticancer therapy, considering hepatic metabolism (liver model) and the assessment of its side effects on a selected organ (skin model). Our research shows that incorporating multiple organ models in one in vitro tool affects the viability and metabolic activity of the cells that constitute them. Moreover, we have shown how important it is to consider hepatic metabolism when evaluating the therapeutic effectiveness of two selected chemotherapy drugs, 5-Fluorouracil (5-FU) and its prodrug Capecitabine (CAP).</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111460"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to testicular damage and impaired spermatogenesis in Wilson disease.","authors":"Dan Zhao, Limin Wu, Xinru Fang, Luyao Wang, Qianzhuo Liu, Pengyu Jiang, Zhihui Ji, Nian Zhang, Miaozhu Yin, Hui Han","doi":"10.1016/j.cbi.2024.111060","DOIUrl":"10.1016/j.cbi.2024.111060","url":null,"abstract":"<p><p>Copper is a toxic heavy metal that causes various damage when it accumulates in the body beyond the physiological threshold. Wilson disease (WD) is an inherited disorder characterized by impaired copper metabolism. Reproductive damage in male patients with WD is gradually attracting attention. However, the underlying mechanisms of copper toxicity are unclear. In this study, we investigated the role of inflammation and PANoptosis in testicular damage and impaired spermatogenesis caused by copper deposition using the WD model toxic milk (TX) mice. Copper chelator-penicillamine and toll-like receptor 4 (TLR4) inhibitor-eritoran were used to intervene in TX mice in our animal experiment methods. Testis samples were collected from mice for further analysis. The results showed that the morphology and ultrastructure of the testis and epididymis in TX mice were damaged, and the sperm counts decreased significantly. The TLR4/nuclear factor kappa-B (NF-κB) signaling pathway was activated by copper deposition, which led to the upregulation of serum and testicular inflammatory factors in TX mice. Meanwhile, pyroptosis, apoptosis, and necroptosis were significant in the testis of TX mice. Both chelated copper or inhibited TLR4 expression markedly suppressed the TLR4/NF-κB signaling pathway, thereby reducing the expression of inflammatory factors. PANoptosis in the testis of TX mice was also reversed. Our study indicated that pathological copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to toxic testicular damage and impaired spermatogenesis in WD.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111060"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the Molecular Mechanisms of Pterostilbene Against Cervical Cancer Through an Integrated Bioinformatics and Network Pharmacology Approach","authors":"Xiang Li, Dequan Yu, Qiming Wang, Yating Chen, Hanbing Jiang","doi":"10.1016/j.cbi.2024.111058","DOIUrl":"https://doi.org/10.1016/j.cbi.2024.111058","url":null,"abstract":"","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":"58 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141039406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of anti-hyperglycemic and anti-hyperlipidemic effects of thiazolidine-2,4-dione derivatives in HFD-STZ diabetic animal model","authors":"S. Fettach, Fatima Zahra Thari, Khalid Karrouchi, Laila Benbacer, Learn-Han Lee, Abdelhakim Bouyahya, Y. Cherrah, Hassan Sefrioui, Khalid Bougrin, M. El Abbes Faouzi","doi":"10.1016/j.cbi.2024.110902","DOIUrl":"https://doi.org/10.1016/j.cbi.2024.110902","url":null,"abstract":"","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139829336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of VRK1 alters the nuclear phosphoproteome in the DNA damage response to doxorubicin","authors":"Elena Navarro-Carrasco, Aurora Campos-Díaz, Eva Monte-Serrano, F. Rolfs, Richard de Goeij-de Haas, T. Pham, S. Piersma, Connie R. Jimenez, Pedro A. Lazo","doi":"10.1016/j.cbi.2024.110908","DOIUrl":"https://doi.org/10.1016/j.cbi.2024.110908","url":null,"abstract":"","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":"14 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139873725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotoxicity of Pyrethroids in exacerbating neurodegenerative diseases: From animals' models to humans’ studies","authors":"Rafael Arsuffi-Marcon, Lizandra Gomes Souza, Artur Santos-Miranda, J. Joviano-Santos","doi":"10.1016/j.cbi.2024.110911","DOIUrl":"https://doi.org/10.1016/j.cbi.2024.110911","url":null,"abstract":"","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":"67 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139817040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}