Chemico-biological interactions最新文献

{"title":"Antigen B from Echinococcus granulosus regulates macrophage phagocytosis by controlling TLR4 endocytosis in immune thrombocytopenia.","authors":"Yunfei Zhang, Yingbin Yue, Yongfeng Cheng, Hongjie Jiao, Mei Yan","doi":"10.1016/j.cbi.2024.111350","DOIUrl":"10.1016/j.cbi.2024.111350","url":null,"abstract":"<p><p>Immune thrombocytopenia (ITP) is characterized by a reduction in platelet counts, stemming from an autoimmune-mediated process where platelets are excessively cleared by macrophages. This enhanced phagocytosis is a cardinal pathogenic mechanism in ITP. Antigen B (AgB), a principal component of the Echinococcus granulosus cyst fluid, plays a pivotal role in safeguarding the parasite from host immune defenses by modulating macrophage activation. In this study, we explored the potential of AgB to regulate macrophage activation in the context of ITP. Our observations indicated a diminished presence of M1 macrophages and a reduced phagocytic capacity in patients infected with E. granulosus sensu stricto. We isolated AgB from E. granulosus cyst fluid (EgCF) and discovered that it could suppress the polarization of M1 macrophages and weaken their phagocytic activity via Fcγ receptors, consequently alleviating thrombocytopenia in an ITP mouse model. At the molecular level, AgB was found to suppress the activation of nuclear factor kappa B (NF-κB) and interferon regulatory factor 3 (IRF3) by impeding their nuclear translocation, leading to a reduction in the generation of inflammatory cytokines. Furthermore, AgB was shown to inhibit Toll-like receptor 4 (TLR4) endocytosis and the recycling of CD14. In aggregate, our findings uncover a novel immunomodulatory mechanism of AgB, which suppresses macrophage phagocytosis by regulating TLR4 endocytosis and the subsequent activation of NF-κB and IRF3 signaling pathways. These insights shed new light on the molecular intricacies of E. granulosus-induced immune evasion and suggest that AgB may serve as a promising therapeutic agent for ITP.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111350"},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824936","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":"Ubiquitin-conjugating enzyme E2T confers chemoresistance of colorectal cancer by enhancing the signal propagation of Wnt/β-catenin pathway in an ERK-dependent manner.","authors":"Bo Liu, Ruiting Liu, Xiaolong Zhang, Lifei Tian, Zeyu Li, Jiao Yu","doi":"10.1016/j.cbi.2024.111347","DOIUrl":"10.1016/j.cbi.2024.111347","url":null,"abstract":"<p><p>Chemotherapy is a major therapeutic option for colorectal cancer; however, the frequently acquired chemoresistance greatly limits the treatment efficacy of chemotherapeutic agents. Ubiquitin-conjugating enzyme E2T (UBE2T) is emerging as a key player in the development of therapy resistance. However, whether UBE2T participates in the acquisition of chemoresistance in colorectal cancer remains undetermined. The present work aimed to specify the role of UBE2T in the development of chemoresistance in colorectal cancer and decipher any potential underlying mechanisms. Significant up-regulation of UBE2T was observed in the clinical specimens of chemoresistant colorectal cancer patients compared with chemosensitive patients. Compared with parental cells, the levels of UBE2T were also dramatically elevated in oxaliplatin (OXA)- and 5-fluorouracil (5-FU)-resistant colorectal cancer cells. Knockout of UBE2T rendered OXA- and 5-FU-resistant cells sensitive to OXA and 5-FU, respectively. Re-expression of UBE2T restored the chemoresistance of UBE2T-knockout OXA- and 5-FU-resistant cells. Mechanistically, phosphorylated GSK-3β, active β-catenin, c-myc and cyclin D1 levels were decreased in UBE2T-knockout OXA- and 5-FU-resistant cells, which were reversed by the re-expression of UBE2T. Moreover, knockout of UBE2T reduced the activation of ERK. The inhibition of ERK reversed the promotion effect of UBE2T on Wnt/β-catenin pathway. In vivo xenograft experiments demonstrated that knockout of UBE2T rendered the subcutaneous tumors formed by OXA-resistant cells sensitive to OXA. To conclude, UBE2T confers chemoresistance of colorectal cancer by boosting the signal propagation of the Wnt/β-catenin pathway in an ERK-dependent manner. Therefore, UBE2T could be a potential target for overcoming chemoresistance in the treatment of colorectal cancer.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111347"},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819987","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":"Evaluation of agonistic and antagonistic effects of unprenylated and prenylated flavonoids on estrogen receptor-α.","authors":"Wonhee Kim, Yujeong Kim, Da-Hyun Jeong, Somin Yi, Hee-Seok Lee, Jun Ho Kim","doi":"10.1016/j.cbi.2024.111346","DOIUrl":"10.1016/j.cbi.2024.111346","url":null,"abstract":"<p><p>Prenylation, which involves the addition of hydrophobic molecules, is considered to enhance the bioavailability and biological activity of flavonoids. However, the effect of prenylation on the estrogenic activity of flavonoids with different structures remains unclear. This study evaluated the estrogen receptor-α (ER-α) agonistic and antagonistic activities of estrogenic flavonoids in both unprenylated and prenylated forms using OECD standardized in vitro ER-α transactivation assay and in vivo uterine hypertrophy assay. A luciferase reporter assay using ER-α-HeLa-9903 cells revealed that twelve flavonoid compounds exhibited ER-α agonistic activity, and among them, only 6-prenylnaringenin (6-PN) exhibited ER-α antagonistic activity. Interestingly, except for 6-PN, prenylated flavonoids showed reduced or similar ER-α agonistic activity compared to their parent compounds. 6-PN, but not 8-prenylnaringenin, demonstrated both enhanced ER-α agonistic and antagonistic activity compared to its parent compound, naringenin. Among the tested compounds, coumestrol exhibited the most potent ER-α agonistic activity in both transactivation and uterotrophic assays. The uterotrophic effect of coumestrol at a dose of 25 mg/kg was stronger than that of 17β-estradiol at 200 μg/kg, as evidenced by changes in uterine weight and estrogen-responsive protein expression. These findings provide important insights into the relative estrogenic potency of flavonoids and the impact of prenylation on their activity.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111346"},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819971","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":"Do the hormetic effects of chlorogenic acid mediate some of the beneficial effects of coffee?","authors":"Edward J Calabrese, Peter Pressman, A Wallace Hayes, Linda Baldwin, Evgenios Agathokleous, Gaurav Dhawan, Rachna Kapoor, Vittorio Calabrese","doi":"10.1016/j.cbi.2024.111343","DOIUrl":"10.1016/j.cbi.2024.111343","url":null,"abstract":"<p><p>The present paper provides the first documentation and assessment of the capacity of chlorogenic acid to induce hormetic dose-response relationships. The findings suggest that chlorogenic acid may induce anabolic (i.e., growth) and catabolic (i.e., protective) hormetic dose responses in several cell types via a range of complementary and cross-talking pathways, affecting a spectrum of endpoints of biomedical and therapeutic importance. This paper also addresses the issue of whether the widely recognized beneficial effects of coffee consumption, as reported in multiple epidemiological studies, may be related to the hormetic effects of chlorogenic acid and its metabolites and their interactions. The present analysis suggests that some beneficial effects of coffee consumption may be due to the effects of chlorogenic acid and/or its metabolites on the gastrointestinal tract via their capacity to impact gastrointestinal integrity, structure, and functionality. These effects collectively contribute to the attenuation of the gastrointestinal tract and concurrent systemic oxidative stress, positively affecting a range of organ-specific effects.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111343"},"PeriodicalIF":0.0,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808719","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":"Squaric acid derivatives with cytotoxic activity-a review.","authors":"Georgi Tirolski, Georgi Momekov, Emiliya Cherneva","doi":"10.1016/j.cbi.2024.111344","DOIUrl":"10.1016/j.cbi.2024.111344","url":null,"abstract":"<p><p>3,4-Dihydroxycyclobut-3-ene-1,2-dione (squaric acid, SQ) is the most important representative of the oxocarbon acids family. Squaric acid derivatives can be promising pharmaceutical agents, due to their unique structural properties, from which novel drugs benefit: a planar aromatic ring, the ability to form hydrogen bonds, good reactivity and similarity with carboxylate, phosphate and amide groups. These properties make it suitable for three major applications in cancer treatment. Firstly, due to their excellent ion binding ability, the halogenated squaramides can be used as artificial ion transporters or mobile carriers to disrupt Na⁺/Cl^- gradients in cancer cells, thus hindering lysosomal function and inducing apoptosis. Another advantage of this class is their bioisosteric properties. Such molecules have been reported to be selective inhibitors of HDACs, FAK, SNM1A, MMP and kinases, involved in tumor growth and metastasis. Finally, the cyclobutenedione moiety proves to be a great linker in complex radiopharmaceuticals, used in theranostics. Its aromaticity and good reactivity make the generation and stability of these drugs easy and efficient. Multiple derivatives containing the squamide motif have been the subject of in-vitro investigations and have demonstrated anti-cancer activity in the nanomolar range against tumor cell lines, including colorectal adenocarcinoma, breast cancer, gastric carcinoma and cervical cancer. On the other hand, squaric acid derivative-Navarixin, has already been evaluated in Phase II clinical trials for its potential efficacy in the treatment of solid tumors. In this context this review is the first looking into the potential applications of squaric acid derivatives as anticancer therapies. It analyzes experimental studies presented in articles published between 2000 and 2024.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111344"},"PeriodicalIF":0.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796633","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":"Critical considerations for co-administering rivaroxaban and vonoprazan: Unveiling potential pharmacokinetic interactions.","authors":"Xiao-Yu Xu, Zhe-Yan Zhang, Xiao-Dan Zhang, Jian-Chao Luo, Yun-Shan Zhong, Le-Hao Jin, Da-Peng Dai, Jian-Chang Qian","doi":"10.1016/j.cbi.2024.111342","DOIUrl":"10.1016/j.cbi.2024.111342","url":null,"abstract":"<p><p>To study the effects of metabolic enzyme activity inhibition and genetic polymorphisms on the pharmacokinetics and pharmacodynamics of rivaroxaban, we established an in vitro enzymatic reaction system to screen for inhibitors, and used the UPLC-MS/MS method to detect the levels of rivaroxaban and its metabolite M2-1. Additionally, in vivo pharmacokinetic-pharmacodynamic studies were conducted using Sprague-Dawley rats. Human recombinant CYP2J2 baculosomes were prepared using a baculovirus-insect expression system to investigate the impact of genetic polymorphisms on rivaroxaban metabolism through enzyme kinetics methods. The results demonstrated that acid-suppressing drugs strongly inhibited the metabolism of rivaroxaban in vitro. Among them, vonoprazan significantly increased the systemic exposure of rivaroxaban in vivo, while also prolonging prothrombin time, likely due to the competitive binding of vonoprazan and rivaroxaban to CYP2J2. Moreover, the genetic polymorphisms of CYP2J2 determined the metabolic characteristics of rivaroxaban and the inhibitory potency of vonoprazan. Overall, our findings suggest that vonoprazan-induced inhibition of CYP2J2 activity can affect the pharmacokinetics and pharmacodynamics of rivaroxaban, with the extent of inhibition determined by the genetic polymorphism of CYP2J2. These insights have important implications for the precise management of rivaroxaban in humans.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111342"},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792553","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":"Deferoxamine-induced neurotoxicity: Role of chaperone-mediated autophagy dysfunction in neuronal apoptosis in the hippocampus.","authors":"Hong Zhang, Jian Guo, Jiayi Chu, Huanhuan Yu, Jialin Zhang, Siman Ma, Ge Jin, Yingshan Jiang, Jiao Xiao, Yutong Hou, Minyan Li, Shiliang Yin","doi":"10.1016/j.cbi.2024.111341","DOIUrl":"10.1016/j.cbi.2024.111341","url":null,"abstract":"<p><p>Deferoxamine mesylate (DFX) is a microorganism-derived iron chelator used in hematology to treat acute iron intoxication and chronic iron overload. Many studies have reported adverse neurological events from DFX exposure, but it is challenging to distinguish these from the effects of iron intoxication. This study aimed to evaluate whether DFX exposure alone can directly impair neurological functions and to elucidate its toxicological mechanisms. Our findings from in vivo and in vitro experiments indicate that DFX exposure can directly cause emotional and cognitive dysfunction in mice. Neuronal apoptosis, resulting from chaperone-mediated autophagy (CMS) dysfunction, was identified as a key toxicological mechanism underlying DFX-induced neuronal impairment. This study provides evidence for the comprehensive monitoring and timely management of neurotoxic adverse events associated with DFX exposure, as well as a foundation for developing medications to prevent and treat these events to enhance patient quality of life.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111341"},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792678","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":"Mitochondria-Targeting Fluorescent Probes for Hydrogen Sulfide Detection and Imaging.","authors":"Yi-Wen Zhu, Ebenezeri Erasto Ngowi, Ao-Qi Tang, Ti Chu, Yan Wang, Zulfa Ismail Shabani, Lucas Paul Luchemba, Tong Jiang, Xin-Ying Ji, Dong-Dong Wu","doi":"10.1016/j.cbi.2024.111328","DOIUrl":"https://doi.org/10.1016/j.cbi.2024.111328","url":null,"abstract":"<p><p>Hydrogen sulfide (H₂S) is a potent redox-active signaling molecule commonly dysregulated in disease states. The production of H₂S and its involvement in various pathological conditions associated with mitochondrial dysfunction has been extensively documented. During stress, cystathionine gamma-lyase and cystathionine beta-synthase enzymes residing in cytosol are copiously translocated into the mitochondria to boost H₂S production, confirming its pivotal role in mitochondrial activities. However, report on H₂S levels in tissue, cells and organelles are lacking, mainly due to the absence of precise and accurate detection tools. Thus, there is a need to determine and monitor the levels of H₂S in this important organelle. Recently, fluorescent probes have been identified as efficient tools for detecting and monitoring the levels of various biomolecules of medical importance including biological thiols. The development of fluorescent probes is a multi-pronged approach involving coupling of fluorophores with responsive sites. The use of fluorescent probes for monitoring mitochondrial H₂S levels has recently received more attention, resulting in numerous publications depicting their synthesis, mechanism of action, application, and potential challenges. Fluorescent probes offer precise and timely results, high sensitivity, and selectivity, low biotoxicity, and minimal background interference. In this review, we aim to report designs of such probes, reaction mechanisms and their application in detecting mitochondrial H₂S levels. Fluorescent probes can help uncover physio/pathological levels of H₂S in essential organelles, its interactions with various biomarkers and associated consequences in biological systems.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111328"},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788099","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":"The role of HIF-1α/BNIP3/mitophagy in acrylonitrile-induced neuronal death in HT22 cells and mice: A potential neuroprotection target.","authors":"Jing Hu, Bobo Yang, Zehua Tao, Jian Chen, Xinyu Zhang, Suhua Wang, Guangwei Xing, Ngwa Adeline Ngeng, Abdul Malik, Kwaku Appiah-Kubi, Marcelo Farina, Anatoly V Skalny, Alexey A Tinkov, Michael Aschner, Rongzhu Lu","doi":"10.1016/j.cbi.2024.111327","DOIUrl":"10.1016/j.cbi.2024.111327","url":null,"abstract":"<p><p>Acrylonitrile (AN) is a widely utilized organic compound in the production of diverse industrial synthetic materials. While acute exposure to AN can cause neurotoxicity, the precise mechanism remains unclear. Hypoxia-inducible factor 1 alpha (HIF-1α) is a pivotal transcription factor that coordinates and orchestrates multiple physiological processes to adapt to hypoxic conditions, ensuring cellular survival and homeostasis. In this study, we used in vitro (cultured mouse hippocampal neuronal cell line, HT22) and in vivo (AN exposed mice) approaches to investigate the potential modulator effects of HIF-1α in AN-induced neurotoxicity. In vitro, AN exposure caused concentration-dependent toxicity in HT22 cells, which was paralleled by increased Bax levels while decreasing Bcl-2. Exposure to AN resulted in reduced protein levels of HIF-1α, Bcl-2 19-kDa interacting protein 3 (BNIP3), microtubule-associated protein 1 light chain 3 beta (LC3B) and Beclin1, while increased the protein levels of the translocase of outer mitochondrial membrane 20 (TOM20). Furthermore, mitochondrial morphology and function were compromised, suggesting that AN impaired HIF-1α/BNIP3-mediated mitochondrial autophagy and promoted apoptosis. Treatment with a HIF-1α activator, cobalt chloride (CoCl₂), reversed these effects, while pretreatment with a HIF-1α inhibitor, 2-methoxyestradiol (2-MeOE2), augmented them. In BNIP3 overexpressing HT22 cells, enhanced cell viability and reduced apoptosis rates were observed. Furthermore, the HIF-1α/BNIP3 pathway was activated by the prolyl hydroxylase (PHD2) inhibitor, deferoxamine (DFO), which increased HT22 cell viability. Similarly, the activation of HIF-1α by administering 20 mg/kg of CoCl₂ was found to alleviate neurotoxicity in mice. This treatment enhanced elevations of autophagy protein expression and co-localization of BNIP3 and LC3B. In summary, under normoxia, AN induced neurotoxicity by promoting PHD2-mediated HIF-1α degradation, disrupted the BNIP3-mediated mitophagy pathway, and enhanced apoptosis. Our findings underscore the effect of the HIF-1α/BNIP3-mediated mitochondrial autophagy in AN-induced neurotoxicity and suggest potential therapeutic strategies involving HIF-1α activation or BNIP3 overexpression for AN poisoning treatment.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111327"},"PeriodicalIF":0.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775451","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":"The effect of a varying pyridine ligand on the anticancer activity of Diiron(I) bis-cyclopentadienyl complexes.","authors":"Annachiara Rossi, Lorenzo Biancalana, Ján Vančo, Tomáš Malina, Stefano Zacchini, Zdeněk Dvořák, Zdeněk Trávníček, Fabio Marchetti","doi":"10.1016/j.cbi.2024.111318","DOIUrl":"10.1016/j.cbi.2024.111318","url":null,"abstract":"<p><p>The new diiron complexes [Fe₂Cp₂(CO)(L)(μ-CO){μ-CN(Me)(Cy)}]CF₃SO₃ (L = pyridine, 3a; 4-aminopyridine, 3b; 4-dimethylaminopyridine, 3c; 4-trifluoromethylpyridine, 3d; nicotinic acid, 4; Cp = η⁵-C₅H₅, Cy = C₆H₁₁ = cyclohexyl) were synthesized in moderate to high yields using two distinct synthetic routes from the precursors 1 (L = CO, for 4) and 2 (L = NCMe, for 3a-d), respectively. All products were characterized by IR and multinuclear NMR spectroscopy, and the structures of 3b and 3d were ascertained by X-ray diffraction studies. The behavior of the complexes in aqueous solutions (solubility, Log P_ow, stability) was assessed using NMR and UV-Vis methods. The in vitro antiproliferative activity of 3a-c and 4 was evaluated against seven human cancer cell lines (A2780, A2780R, A549, MCF-7, PC3, HOS and HT-29) and one normal cell line (MRC-5), following 24 h of incubation (MTT test). Overall, 3-4 demonstrated stronger cytotoxicity than cisplatin, with 3c emerging as the most potent compound. The activity seems primarily linked to the inhibition of metabolic processes in the cancer cells, including depletion of reactive oxygen species (ROS) levels. However, subtle differences have been observed between the complexes, with 4 exerting its cytotoxicity through a distinct multimodal mechanism.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111318"},"PeriodicalIF":0.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741161","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}