Journal of Inorganic Biochemistry最新文献

{"title":"Targeting bacterial efflux pump effectively enhances the efficacy of Ru-based antibacterial agents against Gram-negative pathogen","authors":"Yun Song ,&nbsp;Jing Wang ,&nbsp;Yajun Sun ,&nbsp;Shijia Dong ,&nbsp;Guangying Yu ,&nbsp;Wenjing Lin ,&nbsp;Yinhua Xiong ,&nbsp;Yanhui Tan ,&nbsp;Yanshi Xiong ,&nbsp;Guijuan Jiang ,&nbsp;Jintao Wang ,&nbsp;Xiangwen Liao ,&nbsp;Lianghong Liu","doi":"10.1016/j.jinorgbio.2024.112772","DOIUrl":"10.1016/j.jinorgbio.2024.112772","url":null,"abstract":"<div><div>The rise of antibiotic resistance has posed a great threat to human's life, thus develop novel antibacterial agents is urgently needed. It worthies to noted that Ru-based antibacterial agents often showed robust potency against Gram-positive pathogens, disrupted bacterial membrane and avoided bacterial resistance, making they promising antibiotic candidates. However, they are generally less active when applied to negative pathogens. To address this problem, a Ru-based metalloantibiotic (<strong>RuN</strong>) modified with a nitrothiophene moiety, which can target bacterial efflux pump, was designed and evaluated in this work. A series of assays demonstrated that <strong>RuN</strong> not only fully retained the advantages of Ru-based agents, such as destroyed bacterial membrane and induced reactive oxygen species production, but also can targeted bacterial efflux pumps. Of course, these properties make it effective in killing both Gram-positive and negative pathogens, its MIC values against <em>Staphylococcus aureus</em> and <em>Escherichia coli</em> lies at 3.125 and 6.25 μg/mL, respectively. Importantly, <strong>RuN</strong> also showed low toxicity and has robust anti-infective potency in two animal infection models. Together, our results paved an alternative way to enhance the anti-infective efficacy of Ru-based agents against resistant negative bacteria.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"263 ","pages":"Article 112772"},"PeriodicalIF":3.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring divalent metal ion coordination. Unraveling binding modes in Staphylococcus aureus MntH fragments","authors":"Valentyn Dzyhovskyi ,&nbsp;Maurizio Remelli ,&nbsp;Kamila Stokowa-Sołtys","doi":"10.1016/j.jinorgbio.2024.112769","DOIUrl":"10.1016/j.jinorgbio.2024.112769","url":null,"abstract":"<div><div>Metal ion coordination is crucial in bacterial metabolism, while divalent metal ions serve as essential cofactors for various enzymes involved in cellular processes. Therefore, bacteria have developed sophisticated regulatory mechanisms to maintain metal homeostasis. These involve protein interactions for metal ion uptake, efflux, intracellular transport, and storage. <em>Staphylococcus aureus</em>, a member of the commensal flora, colonizes the anterior nares and skin harmlessly but can cause severe illness. MntH transporter is responsible for acquiring divalent metal ions necessary for metabolic functions and virulence. It is a 450-amino-acid protein analogous to Nramp1 (Natural Resistance-Associated Macrophage Protein 1) in mammals. Herein, the coordination modes of copper(II), iron(II), and zinc(II) ions with select fragments of the MntH were established employing potentiometry, mass spectrometry, and spectroscopic methods. Four model peptides, MNNKRHSTNE–NH₂, Ac-KFDHRSS–NH₂, Ac-IMPHNLYLHSSI–NH₂, and Ac-YSRHNNEE–NH₂, were chosen for their metal-binding capabilities and examined to determine their coordination properties and preferences. Our findings suggest that under physiological pH conditions, the N-terminal fragment of MntH demonstrates the highest thermodynamic stability with copper(II) and iron(II) ions. Furthermore, a comparison with other peptides from the <em>S. aureus</em> FeoB transporter indicates different binding affinities.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"263 ","pages":"Article 112769"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quinoline- and coumarin-based ligands and their rhenium(I) tricarbonyl complexes: synthesis, spectral characterization and antiproliferative activity on T-cell lymphoma","authors":"Martina Piškor ,&nbsp;Ivan Ćorić ,&nbsp;Berislav Perić ,&nbsp;Katarina Mišković Špoljarić ,&nbsp;Srećko I. Kirin ,&nbsp;Ljubica Glavaš-Obrovac ,&nbsp;Silvana Raić-Malić","doi":"10.1016/j.jinorgbio.2024.112770","DOIUrl":"10.1016/j.jinorgbio.2024.112770","url":null,"abstract":"<div><div>Novel 6-substituted 2-(trifluoromethyl)quinoline <strong>5a</strong>–<strong>5e</strong> and coumarin <strong>6a</strong>–<strong>6d</strong> ligands with aldoxime ether linked pyridine moiety were synthesized by <em>O</em>-alkylation of quinoline and coumarin with (<em>E</em>)-picolinaldehyde oxime and subsequently with [Re(CO)₅Cl] gave rhenium(I) tricarbonyl complexes <strong>5a</strong>_{<strong>Re</strong>}–<strong>5e</strong>_{<strong>Re</strong>} and <strong>6a</strong>_{<strong>Re</strong>}–<strong>6d</strong>_{<strong>Re</strong>} that were fully characterized by NMR, single-crystal X-ray diffraction, IR and UV–Vis spectroscopy. The results of antiproliferative evaluation of quinoline and coumarin ligands and their rhenium(I) tricarbonyl complexes on various human tumor cell lines, including acute lymphoblastic leukemia (CCRF-CEM), acute monocytic leukemia (THP1), cervical adenocarcinoma (HeLa), colon adenocarcinoma (CaCo-2), T-cell lymphoma (HuT78), and non-tumor human fibroblasts (BJ) showed that the quinoline complexes <strong>5a</strong>_{<strong>Re</strong>}–<strong>5e</strong>_{<strong>Re</strong>} had higher inhibitory activity than coumarin complexes <strong>6a</strong>_{<strong>Re</strong>}–<strong>6d</strong>_{<strong>Re</strong>}, particularly against T-cell lymphoma (HuT78) cells. 6-Methoxy-2-(trifluoromethyl)quinoline <strong>5e</strong> and 6-methylcoumarin <strong>6d</strong>, and their rhenium(I) tricarbonyl complexes <strong>5e</strong>_{<strong>Re</strong>} and <strong>6d</strong>_{<strong>Re</strong>} were found to arrest the cell cycle of HuT78 cells by causing a significant accumulation of cells in the G0/G1 phase and a marked decrease in the number of cells in the G2/M phase. These rhenium(I) tricarbonyl complexes also slightly increased ROS production and significantly decreased the mitochondrial membrane potential by 50 % (<strong>5e</strong>_{<strong>Re</strong>}) and 45 % (<strong>6d</strong>_{<strong>Re</strong>}) compared to untreated cells and cells treated with <strong>5e</strong> and <strong>6d</strong>. These results suggest that the cytotoxic effects of these compounds are mediated by their effects on mitochondrial membrane potential and the subsequent increase in ROS production.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"262 ","pages":"Article 112770"},"PeriodicalIF":3.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antitumor studies evaluation of triphenylphosphine ruthenium complexes with 5,7-dihalo-substituted-8-quinolinoline targeting mitophagy pathways","authors":"Zhen-Feng Wang ,&nbsp;Xiao-Qiong Huang ,&nbsp;Run-Chun Wu ,&nbsp;Yu Xiao ,&nbsp;Shu-Hua Zhang","doi":"10.1016/j.jinorgbio.2023.112361","DOIUrl":"10.1016/j.jinorgbio.2023.112361","url":null,"abstract":"<div><p><span><span>Both ruthenium-containing complexes and 8-quinolinoline compounds have emerged as a potential novel agent for malignant tumor therapy. Here, three triphenylphosphine </span>ruthenium complexes, [Ru(ZW1)(PPh</span>₃)₂Cl₂] (PPh₃ = triphenylphosphine) (<strong>RuZ1</strong>), [Ru(ZW2)(PPh₃)₂Cl₂] (<strong>RuZ2</strong>) and [Ru(ZW2)₂(PPh₃)Cl₂]·CH₂Cl₂ (<strong>RuZ3</strong><span>) bearing 5,7-dichloro-8-quinolinol (H-ZW1) and 5,7-dichloro-8-hydroxyquinaldine (H-ZW2), have been synthesized, characterized and tested for their anticancer potential. We showed that triphenylphosphine ruthenium complexes </span><strong>RuZ1</strong>–<strong>RuZ3</strong><span> impaired the cell viability<span> of ovarian adenocarcinoma cisplatin-resistant SK-OV-3/DDP (SKO3CR) and SK-OV-3 (SKO3) cancer cells with greater selectivity and specificity than cisplatin. In addition, </span></span><strong>RuZ1</strong>–<strong>RuZ3</strong> show higher excellent cytotoxicity than cisplatin towards SKO3CR cells, with IC₅₀ values of 9.66 ± 1.08, 4.05 ± 0.67 and 7.18 ± 0.40 μM, respectively, in which the SKO3CR cells was the most sensitive to <strong>RuZ1</strong>–<strong>RuZ3</strong>. Depending on the substituent type, the antiproliferative ability of <strong>RuZ1</strong>–<strong>RuZ3</strong> followed the trend: –CH₃ &gt; –H. However, <strong>RuZ1</strong>–<strong>RuZ3</strong> have no obvious toxicity to normal cell HL-7702. Besides, <strong>RuZ1</strong> and <strong>RuZ2</strong><span><span> could induce mitophagy related-apoptosis pathways through suppression of </span>mitochondrial membrane potential (ΔΨm), accumulation of [Ca</span>²⁺<span><span><span>] and reactive oxygen species (ROS), and regulation of LC3 II/LC3 I, Beclin-1, </span>P62<span>, FUNDC1, </span></span>PINK1<span>, Parkin, cleaved-caspase-3, caspase-9 and cytochrome </span></span><em>c</em><span><span><span> signaling pathway, and hindering the preparation of </span>mitochondrial respiration<span> complexes I and IV and ATP levels. </span></span>Mechanistic study revealed that </span><strong>RuZ1</strong> and <strong>RuZ2</strong> induce apoptosis in SKO3CR cells via mitophagy related-apoptosis pathways induction and energy (ATP) generation disturbance. Taken together, the studied triphenylphosphine ruthenium complexes <strong>RuZ1</strong>–<strong>RuZ3</strong> are promising chemotherapeutic agents with high effectiveness and low toxicity.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"248 ","pages":"Article 112361"},"PeriodicalIF":3.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10357382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, characterization, biomolecular interactions, molecular docking, and in vitro and in vivo anticancer activities of novel ruthenium(III) Schiff base complexes","authors":"Milica Međedović ,&nbsp;Aleksandar Mijatović ,&nbsp;Rada Baošić ,&nbsp;Dejan Lazić ,&nbsp;Žiko Milanović ,&nbsp;Zoran Marković ,&nbsp;Jelena Milovanović ,&nbsp;Dragana Arsenijević ,&nbsp;Bojana Stojanović ,&nbsp;Miloš Arsenijević ,&nbsp;Marija Milovanović ,&nbsp;Biljana Petrović ,&nbsp;Ana Rilak Simović","doi":"10.1016/j.jinorgbio.2023.112363","DOIUrl":"10.1016/j.jinorgbio.2023.112363","url":null,"abstract":"<div><p><span>In order to discover new anticancer drugs, novel ruthenium(III) complexes [Ru(</span><em>L</em>)Cl(H₂<span>O)], where L is tetradentate Schiff base </span><em>bis</em>(acetylacetone)ethylendiimine (acacen, <strong>1</strong>), <em>bis</em>(benzoylacetone)ethylendiimine (bzacen, <strong>2</strong>), (acetylacetone)(benzoylaceton)ethylendiimine (acacbzacen, <strong>3</strong>), <em>bis</em>(acetylacetone)propylendiimine (acacpn, <strong>4</strong>), <em>bis</em>(benzoylacetone)propylendiimine (bzacpn, <strong>5</strong>) or (acetylacetone)(benzoylaceton)propylendiimine (acacbzacpn, <strong>6</strong>), were synthesized. The complexes <strong>1 – 6</strong><span> were characterized by elemental analysis<span><span>, molar conductometry, and by various </span>spectroscopic techniques<span>, such as UV–Vis, IR, EPR, and ESI-MS. Based on in vitro DNA/BSA experiments, complexes </span></span></span><strong>2</strong> (bzacen) and <strong>5</strong><span> (bzacpn) with two aromatic rings showed the highest DNA/BSA-activity, suggesting that the presence of the aromatic ring on the tetradentate Schiff base ligand contributes to increased activity. Moreover, these two compounds showed the highest cytotoxic effects toward human, A549 and murine LLC1 lung cancer cells. These complexes altered the ratio of anti- and pro-apoptotic molecules and induced apoptosis of A549 cells. Further, complexes </span><strong>2</strong> and <strong>5</strong><span> reduced the percentage of Mcl1 and Bcl2 expressing LLC1 cells, induced their apoptotic death and exerted an antiproliferative effect against LLC1. Finally, complex </span><strong>5</strong> reduced the volume of mouse primary heterotopic Lewis lung cancer, while complex <strong>2</strong><span> reduced the incidence and mean number of metastases per lung. Additionally, molecular docking<span> with DNA revealed that the reduced number of aromatic rings or their absence causes lower intercalative properties of the complexes in order: </span></span><strong>2 &gt; 5 &gt; 6 &gt; 3 &gt; 4 &gt; 1</strong><span>. It was observed that conventional hydrogen bonds<span> and hydrophobic interactions contribute to the stabilization of the structures of complex-DNA. A molecular docking study with BSA revealed a predominance of </span></span><strong>1 – 6</strong><span> in binding affinity to the active site III, a third </span><em>D</em>-shaped hydrophobic pocket within subdomain IB.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"248 ","pages":"Article 112363"},"PeriodicalIF":3.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10306212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resonance Raman spectra of blue copper proteins: Variable temperature spectra of Thermus thermophilus HB27 laccase","authors":"Janice Kang ,&nbsp;Jieun Shin ,&nbsp;Harry B. Gray,&nbsp;Jay R. Winkler","doi":"10.1016/j.jinorgbio.2023.112362","DOIUrl":"10.1016/j.jinorgbio.2023.112362","url":null,"abstract":"<div><p>The resonance Raman (rR) spectra of the oxidized type 1 copper active site (Cu_T1) in <span><em>Thermus thermophilus</em></span><span> HB27 laccase (</span><em>Tth</em>-lac) has been determined in the 20 to 80 °C temperature range using 633-nm excitation. The positions and relative intensities of rR peaks are virtually independent of temperature, indicating that Cu_T1 ligation is robust over the investigated range. The intensity-weighted average of <em>Tth</em>-lac Cu-S_Cys vibrations (&lt;<em>ν</em>(Cu-S_Cys)&gt;) = 423 cm⁻¹<span>) is higher than those of most cupredoxins but is comparable to those of other multicopper oxidases (MCOs). &lt;</span><em>ν</em>(Cu-S_Cys)&gt; values for <em>Tth</em>-lac and several Cu_T1 centers in cupredoxins and MCOs do not correlate well with Cu-S_Cys bond lengths but do exhibit systematic trends with redox thermodynamic properties.</p></div><div><h3>Prologue</h3><p><span>F. Ann Walker was a great scholar and dear friend. While at Columbia in the early 1960s, I (HBG) followed her graduate work at Brown on the effects of axial ligands on vanadyl ion EPR spectra. Dick Carlin, her thesis adviser, invited me to serve as external member of her thesis committee. I joined, made my way to Providence, met her just before the exam, and greatly admired (enjoyed!) her thoughtful responses to questions from physical chemists about metal-oxo electronic structures. Our friendship grew stronger over the years, enhanced by lively discussions of </span>heme protein<span> chemistry<span> in San Francisco, Pasadena, Tucson, and at Gordon Research Conferences. Ann was a superstar in biological inorganic chemistry. She will be sorely missed but not forgotten.</span></span></p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"248 ","pages":"Article 112362"},"PeriodicalIF":3.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10652348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Cu(II) affinity constant and reactivity of Hepcidin-25, the main iron regulator in human blood","authors":"Dawid Płonka,&nbsp;Marta D. Wiśniewska,&nbsp;Joanna Ziemska-Legięcka,&nbsp;Marcin Grynberg,&nbsp;Wojciech Bal","doi":"10.1016/j.jinorgbio.2023.112364","DOIUrl":"10.1016/j.jinorgbio.2023.112364","url":null,"abstract":"<div><p>Hepcidin is an iron regulatory hormone that does not bind iron directly. Instead, its mature 25-peptide form (<strong>H25</strong>) contains a binding site for other metals, the so-called ATCUN/NTS (amino-terminal Cu/Ni binding site). The Cu(II)-hepcidin complex was previously studied, but due to poor solubility and difficult handling of the peptide the definitive account on the binding equilibrium was not obtained reliably. In this study we performed a series of fluorescence competition experiments between <strong>H25</strong> and its model peptides containing the same ATCUN/NTS site and determined the Cu(II) conditional binding constant of the <strong>CuH25</strong> complex at pH 7.4, ^C<em>K</em>_7.4 = 4 ± 2 × 10¹⁴ M⁻¹. This complex was found to be very inert in exchange reactions and poorly reactive in the ascorbate consumption test. The consequences of these findings for the putative role of Cu(II) interactions with <strong>H25</strong> are discussed.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"248 ","pages":"Article 112364"},"PeriodicalIF":3.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0162013423002465/pdfft?md5=fe9ffebe0b24f730f8ccfe088cecc01b&pid=1-s2.0-S0162013423002465-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10669900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"8-Hydroxyquinoline ruthenium(II) complexes induce ferroptosis in HeLa cells by down-regulating GPX4 and ferritin","authors":"Minying Huang ,&nbsp;Yuqing Zhang ,&nbsp;Yao Gong ,&nbsp;Zhijun Liang ,&nbsp;Xide Chen ,&nbsp;Yunxin Ni ,&nbsp;Xinjie Pan ,&nbsp;Wei Wu ,&nbsp;Jiaxi Chen ,&nbsp;Zunnan Huang ,&nbsp;Jing Sun","doi":"10.1016/j.jinorgbio.2023.112365","DOIUrl":"10.1016/j.jinorgbio.2023.112365","url":null,"abstract":"<div><p><span>Ruthenium<span> complexes are one of the most promising anticancer drugs triggered extensive research. Here, the synthesis and characterization of two ruthenium(II) polypyridine complexes containing 8-hydroxylquinoline as ligand, [Ru(dip)</span></span>₂(8HQ)]PF₆ (<strong>Ru1</strong>), [Ru(dpq)₂(8HQ)]PF₆ (<strong>Ru2</strong><span>) (8HQ = 8-hydroxylquinoline; dip = 4,7-diphenyl-1,10-phenanthroline; dpq = pyrazino[2,3-f][1,10]phenanthroline) were reported. On the basis of cytotoxicity tests, </span><strong>Ru1</strong> (IC₅₀ = 1.98 ± 0.02 μM) and <strong>Ru2</strong> (IC₅₀<span> = 10.02 ± 0.19 μM) both showed good anticancer activity in a panel of cell lines, especially in HeLa cells. Researches on mechanism indicated that </span><strong>Ru1</strong> and <strong>Ru2</strong><span><span><span> acted on mitochondria and nuclei and induced reactive oxygen species (ROS) accumulation, while the morphology of nuclei and cell cycle had no significant change. </span>Western blot assay further proved that </span>GPX4<span> and Ferritin<span> were down-regulated, which eventually triggered ferroptosis in HeLa cells. In addition, the toxicity test of zebrafish embryos showed that the concentrations of </span></span></span><strong>Ru1</strong> and <strong>Ru2</strong> below 120 μM and 60 μM were safe and did not have obvious effect on the normal development of zebrafish embryos.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"248 ","pages":"Article 112365"},"PeriodicalIF":3.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10306215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria-targeted cyclometalated iridium (III) complexes: Dual induction of A549 cells apoptosis and autophagy","authors":"Lanmei Chen ,&nbsp;Hong Tang ,&nbsp;Weigang Chen ,&nbsp;Jie Wang ,&nbsp;Shenting Zhang ,&nbsp;Jie Gao ,&nbsp;Yu Chen ,&nbsp;Xufeng Zhu ,&nbsp;Zunnan Huang ,&nbsp;Jincan Chen","doi":"10.1016/j.jinorgbio.2023.112397","DOIUrl":"10.1016/j.jinorgbio.2023.112397","url":null,"abstract":"<div><p><span>In this study, we synthesized 4 cyclometalated iridium complexes using N-(1,10-phenanthrolin-5-yl)picolinamide (PPA) as the main ligand, denoted as [Ir(ppy)</span>₂PPA]PF₆ (ppy = 2-phenylpyridine, Ir1), [Ir(bzq)₂PPA]PF₆ (bzq = benzo[<em>h</em>]quinoline, Ir2), [Ir(dfppy)₂PPA]PF₆ (dfppy = 2-(3,5-difluorophenyl)pyridine, Ir3), and [Ir(thpy)₂PPA]PF₆<span><span> (thpy = 2-(thiophene-2-yl)pyridine, Ir4). Compared to cisplatin and </span>oxaliplatin, all four complexes exhibited significant anti-tumor activity. Among them, Ir2 demonstrated higher cytotoxicity against A549 cells, with an IC</span>₅₀<span><span> value of 1.6 ± 0.2 μM. The experimental results indicated that Ir2 primarily localized in the mitochondria, inducing a large amount of reactive oxygen species (ROS) generation, that decreased in </span>mitochondrial membrane potential<span><span> (MMP), reduced ATP production, and further impaired mitochondrial function, leading to </span>cytochrome </span></span><em>c</em><span><span><span> release. Additionally, Ir2 caused cell cycle arrest at the S phase and induced apoptosis through the AKT-mediated </span>signaling pathway. Further investigations revealed that Ir2 could simultaneously induce both apoptosis and autophagy in A549 cells, with the latter acting as a non-protective mechanism that promoted cell death. More importantly, Ir2 exhibited low toxicity to both normal LO2 cells in vitro and zebrafish embryos in vivo. Consequently, these newly developed Ir(III) complexes show great potential in the development of novel and low-toxicity </span>anticancer agents.</span></p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"249 ","pages":"Article 112397"},"PeriodicalIF":3.9,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41231213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Jonathan B. Wittenberg (1923–2023)","authors":"Paolo Ascenzi ,&nbsp;Martino Bolognesi ,&nbsp;Michel Guertin ,&nbsp;Luc Moens","doi":"10.1016/j.jinorgbio.2023.112396","DOIUrl":"10.1016/j.jinorgbio.2023.112396","url":null,"abstract":"","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"250 ","pages":"Article 112396"},"PeriodicalIF":3.9,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0162013423002787/pdfft?md5=8058077b5847f131b75f9b767bbecfff&pid=1-s2.0-S0162013423002787-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41187286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}