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Organotin(IV) complexes of tridentate (ONO) hydrazone ligands: synthesis, spectral characterization, antituberculosis, antimicrobial, anti-inflammatory, molecular docking and cytotoxicity studies 三叉(ONO)腙配体的有机锡(IV)配合物:合成、光谱特性、抗结核、抗菌、抗炎、分子对接和细胞毒性研究。
IF 4.1 3区 生物学
Biometals Pub Date : 2024-10-07 DOI: 10.1007/s10534-024-00644-8
Ankit Boora, Jai Devi, Binesh Kumar, Bharti Taxak
{"title":"Organotin(IV) complexes of tridentate (ONO) hydrazone ligands: synthesis, spectral characterization, antituberculosis, antimicrobial, anti-inflammatory, molecular docking and cytotoxicity studies","authors":"Ankit Boora, Jai Devi, Binesh Kumar, Bharti Taxak","doi":"10.1007/s10534-024-00644-8","DOIUrl":"10.1007/s10534-024-00644-8","url":null,"abstract":"<div><p>Infectious diseases have a significant impact in the historical trajectory of humanity, exerting profound influence on societies, driving advancements in medical science, and significantly impacting individuals on a worldwide scale. Consequently, this research endeavours to identify potent agents combatting tuberculosis, inflammation, and microbial deformities. The investigation focuses on hydrazones (1,2) endowed eight organotin(IV) complexes, where hydrazones were derived from 2-acetyl-1H-indene-1,3(2H)-dione and 2-phenoxypropanehydrazide/2-(2,4-dichlorophenoxy)propanehydrazide. All compounds underwent thorough characterization utilizing a variety of spectral and analytical techniques including, multinuclear NMR, FT-IR, HRMS, UV–Vis, SEM-EDAX, TGA, XRD, molar conductance measurements, establishing the pentacoordinated environment around tin(IV) ion with tridentate (ONO) mode of chelation of hydrazones. Powder XRD revealed the ligand's crystalline and complexes' semi-crystalline nature, while thermal analysis indicated two-step decomposition leaving tin oxide residue. In vitro evaluations utilize microplate alamar blue assay for assessing anti-tuberculosis activity, serial dilution technique for antimicrobial efficacy, and bovine serum albumin method for evaluating anti-inflammatory properties. The complexes exhibited higher biological activities than their respective ligands and the activity of the complexes follow the order: Ph<sub>2</sub>SnL<sup>1−2</sup> > Bu<sub>2</sub>SnL<sup>1−2</sup> > Et<sub>2</sub>SnL<sup>1−2</sup> > Me<sub>2</sub>SnL<sup>1−2</sup><sub>.</sub> Among them, phenyl complex (<b>10</b>) [Ph<sub>2</sub>SnL<sup>2</sup>] displays superior efficacy against TB dysfunction (MIC: 0.0180 ± 0.009 μmol/mL) and also demonstrates exceptional potency in combating inflammation (IC<sub>50</sub>: 7.27 ± 0.04 μM), and microbial (MIC: 0.0045 μmol/mL) infections, comparable to standard drugs. Additionally, cytotoxicity testing against vero cell line revealed decreased toxicity at lower concentrations, and attenuated by chelation. Phenyl complex (<b>10</b>) [Ph<sub>2</sub>SnL<sup>2</sup>] shows promising cytotoxicity at 3.12 µg/mL (19.29 ± 0.09%). Further, The diphenyltin(IV) complex (<b>10</b>), identified as the most effective against TB, shows stronger binding to key 3PTY protein residues (− 42.2 kJ/mol) compared to ligand (<b>2</b>) (− 33.4 kJ/mol), correlating with its superior anti-tuberculosis potency in biological assays. This comprehensive approach aims to actively contribute to ongoing initiatives addressing infectious diseases, thereby advancing global health and overall well-being.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div><p>The study synthesized eight organotin(IV) complexes from hydrazones which were derived from 2-acetyl-1H-indene-1,3(2H)-dione and hydrazide derivatives. Complexes demonstrated higher biological activity than their l","PeriodicalId":491,"journal":{"name":"Biometals","volume":"38 1","pages":"153 - 171"},"PeriodicalIF":4.1,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of primary copper metabolism disturbance on elemental, protein, and lipid composition of the organs in Jackson toxic milk mouse 初级铜代谢紊乱对杰克逊毒奶鼠器官元素、蛋白质和脂质组成的影响
IF 4.1 3区 生物学
Biometals Pub Date : 2024-10-04 DOI: 10.1007/s10534-024-00640-y
Krzysztof Hadrian, Magdalena Szczerbowska-Boruchowska, Artur Surówka, Olga Ciepiela, Tomasz Litwin, Adam Przybyłkowski
{"title":"Effect of primary copper metabolism disturbance on elemental, protein, and lipid composition of the organs in Jackson toxic milk mouse","authors":"Krzysztof Hadrian,&nbsp;Magdalena Szczerbowska-Boruchowska,&nbsp;Artur Surówka,&nbsp;Olga Ciepiela,&nbsp;Tomasz Litwin,&nbsp;Adam Przybyłkowski","doi":"10.1007/s10534-024-00640-y","DOIUrl":"10.1007/s10534-024-00640-y","url":null,"abstract":"<div><p>Toxic milk (txJ) is an autosomal recessive mutation in the <i>Atp7b</i> gene in the C3H/HeJ strain, observed at The Jackson Laboratory in Maine, USA. TxJ mice exhibit symptoms similar to those of human Wilson’s disease (WD). The study aimed to verify organ involvement in a mouse model of WD. TxJ mice and control animals were sacrificed at 2, 4, 8, and 14 months of age. Total X-ray Fluorescence Spectroscopy (TXRF) was used to determine the elemental concentration in organs. Tissue chemical composition was measured by Fourier Transform Infrared Spectroscopy (FTIR). Additionally, hybrid mapping of FTIR and microXRF was performed. Elevated concentrations of Cu were observed in the liver, striatum, eye, heart, and duodenum of txJ mice across age groups. In the striatum of the oldest txJ mice, there was lower lipid content and a higher fraction of saturated fats. The secondary structure of striatum proteins was disturbed in txJ mice. In the livers of txJ mice, higher concentrations of saturated fats and disturbances in the secondary structure of proteins were observed. The concentration of neurofilaments was significantly higher in txJ serum. The distribution of Cu deposits in brains was uniform with no prevalence in any anatomic structure in either group, but significant protein structure changes were observed exclusively in the striatum of txJ. In this txJ animal model of WD, pathologic copper accumulation occurs in the duodenum, heart, and eye tissues. Increased copper concentration in the liver and brain results in increased saturated fat content and disturbances in secondary protein structure, leading to hepatic injury and neurodegeneration.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"38 1","pages":"103 - 121"},"PeriodicalIF":4.1,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10534-024-00640-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DFT and TD-DFT studies to elucidate the configurational isomers of ferric aerobactin, ferric petrobactin, and their ferric photoproducts. 通过 DFT 和 TD-DFT 研究阐明铁质气孔菌素、铁质岩石菌素及其铁质光产物的构型异构体。
IF 4.1 3区 生物学
Biometals Pub Date : 2024-10-02 DOI: 10.1007/s10534-024-00638-6
Sasha Gardner, Carl J Carrano, Yuezhi Mao, Frithjof C Küpper, Andrew L Cooksy
{"title":"DFT and TD-DFT studies to elucidate the configurational isomers of ferric aerobactin, ferric petrobactin, and their ferric photoproducts.","authors":"Sasha Gardner, Carl J Carrano, Yuezhi Mao, Frithjof C Küpper, Andrew L Cooksy","doi":"10.1007/s10534-024-00638-6","DOIUrl":"https://doi.org/10.1007/s10534-024-00638-6","url":null,"abstract":"<p><p>Iron-chelating siderophores such as aerobactin and petrobactin are produced by marine bacteria to sequester iron under low iron stress. Those that contain a citrate moiety undergo light-catalyzed ligand-to-metal charge transfer, inducing decarboxylation and formation of photoproducts. In this work, we employed density functional theory to obtain the optimized geometries and determine the relative energies and geometric parameters of different configurations of Fe(III)-coordinated aerobactin, petrobactin, and their photoproducts. Time-dependent density functional theory was then used to compute the UV-Vis absorption spectra of these species, and the comparison against experimental spectra further elucidated the structural configurations most likely to be adopted by these compounds. Frequency calculations provided Fe-O force constants on the same order as other siderophores. The relative energies and predicted spectra support the cis-cis C-fac configuration for ferric aerobactin and the cis-trans C-mer configuration for its photoproduct, while only mild support is found for specific configurations of the ferric petrobactin structures (meta-mer and meta-fac for the precursor, cis-cis para-fac for the photoproduct). The predicted ferric petrobactin spectra are found to be fairly insensitive to the configuration of the ferric complex.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Trace elements and metal nanoparticles: mechanistic approaches to mitigating chemotherapy-induced toxicity—a review of literature evidence 微量元素和金属纳米颗粒:减轻化疗毒性的机理方法--文献证据综述。
IF 4.1 3区 生物学
Biometals Pub Date : 2024-09-30 DOI: 10.1007/s10534-024-00637-7
Ademola C. Famurewa, Mina Y. George, Cletus A. Ukwubile, Sachindra Kumar, Mehta V. Kamal, Vijetha S. Belle, Eman M. Othman, Sreedhara Ranganath K. Pai
{"title":"Trace elements and metal nanoparticles: mechanistic approaches to mitigating chemotherapy-induced toxicity—a review of literature evidence","authors":"Ademola C. Famurewa,&nbsp;Mina Y. George,&nbsp;Cletus A. Ukwubile,&nbsp;Sachindra Kumar,&nbsp;Mehta V. Kamal,&nbsp;Vijetha S. Belle,&nbsp;Eman M. Othman,&nbsp;Sreedhara Ranganath K. Pai","doi":"10.1007/s10534-024-00637-7","DOIUrl":"10.1007/s10534-024-00637-7","url":null,"abstract":"<div><p>Anticancer chemotherapy (ACT) remains a cornerstone in cancer treatment, despite significant advances in pharmacology over recent decades. However, its associated side effect toxicity continues to pose a major concern for both oncology clinicians and patients, significantly impacting treatment protocols and patient quality of life. Current clinical strategies to mitigate ACT-induced toxicity have proven largely unsatisfactory, leaving a critical unmet need to block toxicity mechanisms without diminishing ACT's therapeutic efficacy. This review aims to document the molecular mechanisms underlying ACT toxicity and highlight research efforts exploring the protective effects of trace elements (TEs) and their nanoparticles (NPs) against these mechanisms. Our literature review reveals that the primary driver of ACT toxicity is redox imbalance, which triggers oxidative inflammation, apoptosis, endoplasmic reticulum stress, mitochondrial dysfunction, autophagy, and dysregulation of signaling pathways such as PI3K/mTOR/Akt. Studies suggest that TEs, including zinc, selenium, boron, manganese, and molybdenum, and their NPs, can potentially counteract ACT-induced toxicity by inhibiting oxidative stress-mediated pathways, including NF-κB/TLR4/MAPK/NLRP3, STAT-3/NLRP3, Bcl-2/Bid/p53/caspases, and LC3/Beclin-1/CHOP/ATG6, while also upregulating protective signaling pathways like Sirt1/PPAR-γ/PGC-1α/FOXO-3 and Nrf2/HO-1/ARE. However, evidence regarding the roles of lncRNA and the Wnt/β-catenin pathway in ACT toxicity remains inconsistent, and the impact of TEs and NPs on ACT efficacy is not fully understood. Further research is needed to confirm the protective effects of TEs and their NPs against ACT toxicity in cancer patients. In summary, TEs and their NPs present a promising avenue as adjuvant agents for preventing non-target organ toxicity induced by ACT.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 6","pages":"1325 - 1378"},"PeriodicalIF":4.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lead-induced changes in plant cell ultrastructure: an overview 铅诱导的植物细胞超微结构变化:概述
IF 4.1 3区 生物学
Biometals Pub Date : 2024-09-26 DOI: 10.1007/s10534-024-00639-5
Oumaima El Khattabi, Youssef Lamwati, Fatima Henkrar, Blanche Collin, Clement Levard, Fabrice Colin, Abdelaziz Smouni, Mouna Fahr
{"title":"Lead-induced changes in plant cell ultrastructure: an overview","authors":"Oumaima El Khattabi,&nbsp;Youssef Lamwati,&nbsp;Fatima Henkrar,&nbsp;Blanche Collin,&nbsp;Clement Levard,&nbsp;Fabrice Colin,&nbsp;Abdelaziz Smouni,&nbsp;Mouna Fahr","doi":"10.1007/s10534-024-00639-5","DOIUrl":"10.1007/s10534-024-00639-5","url":null,"abstract":"<div><p>Lead (Pb) is one of the most harmful toxic metals and causes severe damage to plants even at low concentrations. Pb inhibits plant development, reduces photosynthesis rates, and causes metabolic disfunctions. Plant cells display these alterations in the form of abnormal morphological modifications resulting from ultrastructural changes in the cell wall, plasma membrane, chloroplast, endoplasmic reticulum, mitochondria, and nuclei. Depending on plant tolerance capacity, the ultrastructural changes could be either a sign of toxicity that limits plant development or an adaptive strategy to cope with Pb stress. This paper gathers data on Pb-induced changes in cell ultrastructure observed in many tolerant and hyperaccumulator plants and describes the ultrastructural changes that appear to be mechanisms to alleviate Pb toxicity. The different modifications caused by Pb in cell organelles are summarized and reinforced with hypotheses that provide an overview of plant responses to Pb stress and explain the physiological and morphological changes that occur in tolerant plants. These ultrastructural modifications could help assess the potential of plants for use in phytoremediation.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"38 1","pages":"1 - 19"},"PeriodicalIF":4.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cytotoxic and ROS generation activity of anthraquinones chelate complexes with metal ions 蒽醌类化合物与金属离子的螯合物的细胞毒性和 ROS 生成活性。
IF 4.1 3区 生物学
Biometals Pub Date : 2024-09-21 DOI: 10.1007/s10534-024-00632-y
Viktor A. Timoshnikov, Irina A. Slepneva, Olga A. Chinak, Olga Yu Selyutina, Nikolay E. Polyakov
{"title":"Cytotoxic and ROS generation activity of anthraquinones chelate complexes with metal ions","authors":"Viktor A. Timoshnikov,&nbsp;Irina A. Slepneva,&nbsp;Olga A. Chinak,&nbsp;Olga Yu Selyutina,&nbsp;Nikolay E. Polyakov","doi":"10.1007/s10534-024-00632-y","DOIUrl":"10.1007/s10534-024-00632-y","url":null,"abstract":"<div><p>Anthraquinones (AQs) are very effective chemotherapeutic agent, however their fundamental shortcoming is high cardiotoxicity caused by reactive oxygen species (ROS). Therefore, development of improved antitumor drugs with enhanced efficacy but reduced side effects remains a high priority. In the present study we evaluated the cytotoxicity and ROS generation activity of chelate complex of redox-active anthraquinone 2-phenyl-4-(butylamino)naphtho[2,3-h]quinoline-7,12-dione (Q1) with iron and copper ions. Cytotoxicity study was performed using the lung cancer cell line A549 and breast cancer cell line MDA-MB-231. Q1 and Cu-Q1 complex demonstrate high activity in these experiments, but Fe-Q1 complex inactive. The ROS generation activity has been studied by EPR spin trapping technique using A549, MDA-MB-231 cell lines, and T lymphoblast cell line MOLT-4. It was shown that Q1 is able to penetrate into these cells and participate in redox reactions with the formation of a semiquinone radical. Fe(III) chelate complex formation results in much slower kinetics of ROS generation compared with pure Q1, which could be connected with a lower penetration through the cell membrane.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 6","pages":"1643 - 1656"},"PeriodicalIF":4.1,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Leptospira interrogans proteome’s response to zinc highlights the potential involvement of this metal in translational—machinery and virulence 讯号钩端螺旋体蛋白质组对锌的反应突显了这种金属在翻译机械和毒力方面的潜在参与。
IF 4.1 3区 生物学
Biometals Pub Date : 2024-09-21 DOI: 10.1007/s10534-024-00634-w
Amanda Silva Hecktheuer, Cassia Moreira Santos, Fabienne Antunes Ferreira, Angela Silva Barbosa, Lourdes Isaac, Marilis Valle Marques, Ricardo Ruiz Mazzon
{"title":"The Leptospira interrogans proteome’s response to zinc highlights the potential involvement of this metal in translational—machinery and virulence","authors":"Amanda Silva Hecktheuer,&nbsp;Cassia Moreira Santos,&nbsp;Fabienne Antunes Ferreira,&nbsp;Angela Silva Barbosa,&nbsp;Lourdes Isaac,&nbsp;Marilis Valle Marques,&nbsp;Ricardo Ruiz Mazzon","doi":"10.1007/s10534-024-00634-w","DOIUrl":"10.1007/s10534-024-00634-w","url":null,"abstract":"<div><p>Leptospires, as motile Gram-negative bacteria, employ sophisticated strategies for efficient invasion and dissemination within their hosts. In response, hosts counteract pathogens through nutritional immunity, a concept involving the deprivation of essential metals such as zinc. Zinc, pivotal in modulating pathogen-host interactions, influences proteins structural, catalytic, and regulatory functions. A comprehensive understanding of how leptospires regulate intracellular zinc availability is crucial for deciphering their survival mechanisms. This study explores the proteomic profile of <i>Leptospira interrogans</i> sv. Copenhageni str. 10A cultivated in Ellinghausen-McCullough-Johnson-Harris medium supplemented with the zinc chelator TPA or ZnCl<sub>2</sub>. Among the 2161 proteins identified, 488 were subjected to scrutiny, revealing 102 less abundant and 81 more abundant in response to TPA. Of these 488 proteins, 164 were exclusive to the presence of TPA and 141 were exclusive to the zinc-enriched conditions. Differentially expressed proteins were classified into clusters of orthologous groups (COGs) with a distribution in metabolic functions (37.8%), information storage/processing (21.08%), cellular processes/signaling (28.04%), and poorly characterized proteins (10.65%). Differentially expressed proteins are putatively involved in processes like 1-carbon compound metabolism, folate biosynthesis, and amino acid/nucleotide synthesis. Zinc availability significantly impacted key processes putatively related to leptospires’ interactions with their host, such as motility, biofilm formation, and immune escape. Under conditions of higher zinc concentration, ribosomal proteins, chaperones and components of transport systems were observed, highlighting interactions between regulatory networks responsive to zinc and iron in <i>L. interrogans</i>. This study not only revealed hypothetical proteins potentially related to zinc homeostasis, but also identified possible virulence mechanisms and pathogen-host adaptation strategies influenced by the availability of this metal. There is an urgent need, based on these data, for further in-depth studies aimed at detailing the role of zinc in these pathways and mechanisms, which may ultimately determine more effective therapeutic approaches to combat <i>Leptospira</i> infections.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 6","pages":"1677 - 1698"},"PeriodicalIF":4.1,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Experimental and computational evaluation of anti-malarial and antioxidant potential of transition metal (II) complexes with tridentate schiff base derived from pyrrolopyrimidine 过渡金属 (II) 与源自吡咯并嘧啶的三叉片基配合物的抗疟疾和抗氧化潜力的实验和计算评估
IF 4.1 3区 生物学
Biometals Pub Date : 2024-09-13 DOI: 10.1007/s10534-024-00636-8
Abhay D. Bagul, Manish Kumar, Amer M. Alanazi, Aisha Tufail, Nasir Tufail, Digamber D. Gaikwad, Amit Dubey
{"title":"Experimental and computational evaluation of anti-malarial and antioxidant potential of transition metal (II) complexes with tridentate schiff base derived from pyrrolopyrimidine","authors":"Abhay D. Bagul,&nbsp;Manish Kumar,&nbsp;Amer M. Alanazi,&nbsp;Aisha Tufail,&nbsp;Nasir Tufail,&nbsp;Digamber D. Gaikwad,&nbsp;Amit Dubey","doi":"10.1007/s10534-024-00636-8","DOIUrl":"10.1007/s10534-024-00636-8","url":null,"abstract":"<div><p>In the twenty-first century, we are experiencing persistent waves of diverse pathogen variations, contributing significantly to global illness and death rates. Within this varied spectrum of illnesses, malaria and oxidative damage emerge as prominent obstacles that have persistently affected human health. The motivation for exploring the antioxidant potential of transition metal (II) complexes with tridentate Schiff base ligands is driven by the need for effective treatments against malaria and oxidative stress-related conditions. Both malaria and oxidative damage are significant global health concerns. Transition metal complexes can potentially offer enhanced anti-malarial and antioxidant activities, providing a dual benefit. To explore the aforementioned facts and examine the therapeutic potential, the previously synthesized pyrrolopyrimidinehydrazide-3-chlorobenzaldehyde, such as HPPHmCB ligand(1)andtheirMn(II),Fe(II),Co(II),Ni(II), Pd(II),Cu(II),Zn(II),Cd(II),Hg(II)complexes(2–10) of benzaldehydes and pyrrolopyrimidinehydrazide were proposed for in vitro anti-malarial and antioxidant investigation. These compounds were assessed for their anti-malarial efficacy against <i>Plasmodium falciparum</i> using a micro assay protocol, with IC<sub>50</sub> values indicating the concentration required to inhibit parasite maturation by 50%. The Hg(II) complex displays pronounced antimalarial activity with an IC<sub>50</sub> value of 1.98 ± 0.08 µM, closely aligning with the efficacy of quinine, whereas Zn(II), Cu(II), Pd(II) complexes demonstrates most significant anti-malarial activity, with IC<sub>50</sub> values close to the reference compound quinine. The antioxidant activity of the compounds was evaluated using the DPPH assay, with several metal complexes such as Cu(II)and Zn(II) showing strong potential in neutralizing oxidative stress. Furthermore, molecular docking simulations were conducted to explore the binding interactions of the compounds with PfNDH2, providing insights into their pharmacological potential. The study also examined the electronic properties, solubility, and potential hepatotoxicity of the compounds. The findings suggest that the metal complexes could be promising candidates for further development as anti-malarial agents, offering enhanced potency compared to the base compound.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 6","pages":"1713 - 1737"},"PeriodicalIF":4.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Insoluble HIFa protein aggregates by cadmium disrupt hypoxia-prolyl hydroxylase (PHD)-hypoxia inducible factor (HIFa) signaling in renal epithelial (NRK-52E) and interstitial (FAIK3-5) cells 镉的不溶性HIFa蛋白聚集体破坏了肾上皮细胞(NRK-52E)和肾间质细胞(FAIK3-5)中的缺氧-脯氨酰羟化酶(PHD)-缺氧诱导因子(HIFa)信号传导
IF 4.1 3区 生物学
Biometals Pub Date : 2024-09-10 DOI: 10.1007/s10534-024-00631-z
Timm Schreiber, Bettina Scharner, Frank Thévenod
{"title":"Insoluble HIFa protein aggregates by cadmium disrupt hypoxia-prolyl hydroxylase (PHD)-hypoxia inducible factor (HIFa) signaling in renal epithelial (NRK-52E) and interstitial (FAIK3-5) cells","authors":"Timm Schreiber,&nbsp;Bettina Scharner,&nbsp;Frank Thévenod","doi":"10.1007/s10534-024-00631-z","DOIUrl":"10.1007/s10534-024-00631-z","url":null,"abstract":"<div><p>The kidney is the main organ that senses changes in systemic O<sub>2</sub> pressure by hypoxia-PHD-HIFa (HPH) signaling, resulting in adaptive target gene activation, including erythropoietin (EPO). The non-essential transition metal cadmium (Cd) is nephrotoxic and disrupts the renal HPH pathway, which may promote Cd-associated chronic renal disease (CKD). A deeper molecular understanding of Cd interference with renal HPH signaling is missing, and no data with renal cell lines are available. In rat kidney NRK-52E cells, which model the proximal tubule, and murine fibroblastoid atypical interstitial kidney (FAIK3-5) cells, which mimic renal EPO-producing cells, the chemical hypoxia mimetic dimethyloxalylglycine (DMOG; 1 mmol/l) or hypoxia (1% O<sub>2</sub>) activated HPH signaling. Cd<sup>2+</sup> (2.5–20 µmol/l for ≤ 24 h) preferentially induced necrosis (trypan blue uptake) of FAIK3-5 cells at high Cd whereas NRK-52E cells specially developed apoptosis (PARP-1 cleavage) at all Cd concentrations. Cd (12.5 µmol/l) abolished HIFa stabilization and prevented upregulation of target genes (quantitative real-time polymerase chain reaction and immunoblotting) induced by DMOG or hypoxia in both cell lines, which was caused by the formation of insoluble HIFa aggregates. Strikingly, hypoxic preconditioning (1% O<sub>2</sub> for 18 h) reduced apoptosis of FAIK3-5 and NRK-52E cells at low Cd concentrations and decreased insoluble HIFa proteins. Hence, drugs mimicking hypoxic preconditioning could reduce CKD induced by chronic low Cd exposure.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 6","pages":"1629 - 1642"},"PeriodicalIF":4.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10534-024-00631-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142209897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New solvated Mo(VI) complexes of isatin based asymmetric bisthiocarbohydrazones as potent bioactive agent: synthesis, DFT-molecular docking studies, biological activity evaluation and crystal structures 作为强效生物活性剂的异靛基不对称双硫代羧酰肼的新溶解钼(VI)配合物:合成、DFT-分子对接研究、生物活性评价和晶体结构。
IF 4.1 3区 生物学
Biometals Pub Date : 2024-09-06 DOI: 10.1007/s10534-024-00633-x
Yeliz Kaya, Ayşe Erçağ, Savaş Kaya, Avni Berisha, Birnur Akkaya, Yunus Zorlu
{"title":"New solvated Mo(VI) complexes of isatin based asymmetric bisthiocarbohydrazones as potent bioactive agent: synthesis, DFT-molecular docking studies, biological activity evaluation and crystal structures","authors":"Yeliz Kaya,&nbsp;Ayşe Erçağ,&nbsp;Savaş Kaya,&nbsp;Avni Berisha,&nbsp;Birnur Akkaya,&nbsp;Yunus Zorlu","doi":"10.1007/s10534-024-00633-x","DOIUrl":"10.1007/s10534-024-00633-x","url":null,"abstract":"<div><p>New solvated Mo(VI) complexes were isolated from the reaction of [MoO<sub>2</sub>(acac)<sub>2</sub>] with asymmetric isatin bisthiocarbohydrazone ligands. The ligands were obtained from the reaction of isatin monothiocarbohydrazone with 3,5-dibromo salicylaldehyde (L1), 3,5-dichloro salicylaldehyde (L2) and 3-chloro-5-bromo salicylaldehyde (L3), respectively. In the complexes, the ligands serve as ONS donors and coordinate to the [MoO<sub>2</sub>]<sup>2+</sup> nucleus. The bonding sites are azomethine nitrogen atom, phenolic oxygen atom and thiol sulfur atom. The sixth coordination site is completed by an oxygen atom from an ethanol solvent. The ethanol-coordinated Mo(VI) complexes, C1–C3, [MoO<sub>2</sub>L(EtOH)] (L: L1–L3), were characterized using elemental analysis, IR and <sup>1</sup>H NMR spectroscopies, and conductivity measurements. By crystallizing ethanol-solvated solid complexes from an EtOH/DMSO mixture, DMSO-solvated complexes (C4–C6) suitable for X-ray crystallography were obtained. Crystal structure analysis supports the proposed complex structures and geometries, but the ethanol in the sixth coordination site has been replaced by DMSO. When the anticarcinogenic effects of the ligands and complexes (C1–C3) on the C6 cell line were examined, it was found that the complexes showed higher activity than the ligands. The C3 complex appears to have the best anti-cancer activity compared to doxorubicin. Additionally, all compounds were determined to have high total antioxidant capacity. Data obtained from theoretical studies (DFT and docking) support experimental studies.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 6","pages":"1657 - 1675"},"PeriodicalIF":4.1,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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