Journal of Inorganic Biochemistry最新文献

{"title":"Redox-active polyoxovanadates as cofactors in the development of functional protein assemblies","authors":"David E. Salazar Marcano,&nbsp;Jieh-Jang Chen,&nbsp;Mhamad Aly Moussawi,&nbsp;Givi Kalandia,&nbsp;Alexander V. Anyushin,&nbsp;Tatjana N. Parac-Vogt","doi":"10.1016/j.jinorgbio.2024.112687","DOIUrl":"10.1016/j.jinorgbio.2024.112687","url":null,"abstract":"<div><p>The interactions of polyoxovanadates (POVs) with proteins have increasingly attracted interest in recent years due to their potential biomedical applications. This is especially the case because of their redox and catalytic properties, which make them interesting for developing artificial metalloenzymes. Organic-inorganic hybrid hexavanadates in particular offer several advantages over all-inorganic POVs. However, they have been scarcely investigated in biological systems even though, as shown in this work, hybrid hexavanadates are highly stable in aqueous solutions up to relatively high pH. Therefore, a novel bis-biotinylated hexavanadate was synthesized and shown to selectively interact with two biotin-binding proteins, avidin and streptavidin. Bridging interactions between multiple proteins led to their self-assembly into supramolecular bio-inorganic hybrid systems that have potential as artificial enzymes with the hexavanadate core as a redox-active cofactor. Moreover, the structure and charge of the hexavanadate core were determined to enhance the binding affinity and slightly alter the secondary structure of the proteins, which affected the size and speed of formation of the assemblies. Hence, tuning the polyoxometalate (POM) core of hybrid POMs (HPOMs) with protein-binding ligands has been demonstrated to be a potential strategy for controlling the self-assembly process while also enabling the formation of novel POM-based biomaterials that could be of interest in biomedicine.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141978510","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":"Heme pocket hydrogen bonding residue interactions within the Pectobacterium Diguanylate cyclase-containing globin coupled sensor: A resonance Raman study","authors":"Nushrat J. Hoque ,&nbsp;Shannon Rivera ,&nbsp;Paul G. Young ,&nbsp;Emily E. Weinert ,&nbsp;Yilin Liu","doi":"10.1016/j.jinorgbio.2024.112686","DOIUrl":"10.1016/j.jinorgbio.2024.112686","url":null,"abstract":"<div><p>Heme-based sensor proteins are used by organisms to control signaling and physiological effects in response to their gaseous environment. Globin-coupled sensors (GCS) are oxygen-sensing proteins that are widely distributed in bacteria. These proteins consist of a heme globin domain linked by a middle domain to various output domains, including diguanylate cyclase domains, which are responsible for synthesizing <em>c</em>-di-GMP, a bacterial second messenger crucial for regulating biofilm formation. To understand the roles of heme pocket residues in controlling activity of the diguanylate cyclase domain, variants of the <em>Pectobacterium carotovorum</em> GCS (<em>Pcc</em>GCS) were characterized by enzyme kinetics and resonance Raman (rR) spectroscopy. Results of these studies have identified roles for hydrogen bonding and heme edge residues in modulating heme pocket conformation and flexibility. Better understanding of the ligand-dependent GCS signaling mechanism and the residues involved may allow for future development of methods to control O₂-dependent <em>c</em>-di-GMP production.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896402","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":"Repurposing myoglobin into a carbene transferase for a [2,3]-sigmatropic Sommelet-Hauser rearrangement","authors":"Manon Pujol ,&nbsp;Lison Degeilh ,&nbsp;Thibault Sauty de Chalon ,&nbsp;Marius Réglier ,&nbsp;A. Jalila Simaan ,&nbsp;Christophe Decroos","doi":"10.1016/j.jinorgbio.2024.112688","DOIUrl":"10.1016/j.jinorgbio.2024.112688","url":null,"abstract":"<div><p>New-to-Nature biocatalysis has emerged as a promising tool in organic synthesis thanks to progress in protein engineering. Notably, hemeproteins have been evolved into robust catalysts for carbene and nitrene transfers and related sigmatropic rearrangements. In this work, we report the first example of a [2,3]-sigmatropic Sommelet-Hauser rearrangement initiated by a carbene transfer of the sperm whale myoglobin mutant L29S,H64V,V68F that was previously reported to catalyze the mechanistically similar [2,3]-sigmatropic Doyle-Kirmse rearrangement. This repurposed heme enzyme catalyzes the Sommelet-Hauser rearrangement between ethyl diazoacetate and benzyl thioethers bearing strong electron-withdrawing substituents with good yields and enantiomeric excess. Optimized catalytic conditions in the absence of any reductant led to an increased asymmetric induction with up to 59% enantiomeric excess. This myoglobin mutant is therefore one of the few catalysts for the asymmetric Sommelet-Hauser rearrangement. This work broadens the scope of abiological reactions catalyzed by iron-carbene transferases with a new example of asymmetric sigmatropic rearrangement.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900433","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 structure of Mn(II)–bound Rubisco from Spinacia oleracea","authors":"Robert W. Voland,&nbsp;Rachael E. Coleman,&nbsp;Kyle M. Lancaster","doi":"10.1016/j.jinorgbio.2024.112682","DOIUrl":"10.1016/j.jinorgbio.2024.112682","url":null,"abstract":"<div><p>The rate of photosynthesis and, thus, CO₂ fixation, is limited by the rate of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). Not only does Rubisco have a relatively low catalytic rate, but it also is promiscuous regarding the metal identity in the active site of the large subunit. In Nature, Rubisco binds either Mg(II) or Mn(II), depending on the chloroplastic ratio of these metal ions; most studies performed with Rubisco have focused on Mg-bound Rubisco. Herein, we report the first crystal structure of a Mn-bound Rubisco, and we compare its structural properties to those of its Mg-bound analogues.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878154","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":"Polyimidazole ligands: Copper(II) complexes and antiproliferative activity in cancer cells","authors":"Fabrizia Brisdelli ,&nbsp;Noemi Bognanni ,&nbsp;Alessandra Piccirilli ,&nbsp;Mariagrazia Perilli ,&nbsp;Denise Bellotti ,&nbsp;Maurizio Remelli ,&nbsp;Graziella Vecchio","doi":"10.1016/j.jinorgbio.2024.112685","DOIUrl":"10.1016/j.jinorgbio.2024.112685","url":null,"abstract":"<div><p>The design of novel chelators for therapeutic applications has been the subject of extensive research to address various diseases. Many chelators can manipulate the levels of metal ions within cells and effectively modulate the metal excess. In some cases, chelators show significant toxicity to cells.</p><p>We investigated polyimidazole ligands by potentiometry and UV–Vis spectroscopy for their ability to form copper(II) complexes. We also compared the antiproliferative activity of the polyimidazole ligands and their copper(II) complexes with polypyridine ligands in CaCo-2 (colorectal adenocarcinoma), SH-SY5Y (neuroblastoma) and K562 (chronic myelogenous leukemia) cells and normal HaCaT (keratinocyte) cells.</p><p>Polyimidazole ligands are less cytotoxic than their analogous polypyridine ligands. All polyimidazole ligands, except the tetraimidazole ligand for K562 cells, did not show any significant effect on the viability of cancer and normal cells. In contrast, the cytotoxic activity of polypiridine ligands was also observed in normal cells with IC₅₀ values similar to those of cancer cells.</p><p>Tetraimidazole ligand, the only ligand active on the leukemic K562 cell line, induced caspase-dependent apoptosis and increased intracellular reactive oxygen species production with mitochondrial damage.</p><p>The low cytotoxicity of the polyimidazole ligands, even if it limits their use as anticancer agents, could make them useful in other medical applications, such as in the treatment of metal overload, microbial infections, inflammation or neurodegenerative disorders.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0162013424002095/pdfft?md5=75b64fd9593f4abb499e252ad97fd3cd&pid=1-s2.0-S0162013424002095-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141978508","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":"Entrance channels to coproheme in coproporphyrin ferrochelatase probed by exogenous imidazole binding","authors":"Andrea Dali ,&nbsp;Thomas Gabler ,&nbsp;Federico Sebastiani ,&nbsp;Paul G. Furtmüller ,&nbsp;Maurizio Becucci ,&nbsp;Stefan Hofbauer ,&nbsp;Giulietta Smulevich","doi":"10.1016/j.jinorgbio.2024.112681","DOIUrl":"10.1016/j.jinorgbio.2024.112681","url":null,"abstract":"<div><p>Iron insertion into porphyrins is an essential step in heme biosynthesis. In the coproporphyrin-dependent pathway, specific to monoderm bacteria, this reaction is catalyzed by the monomeric enzyme coproporphyrin ferrochelatase. In addition to the mechanistic details of the metalation of the porphyrin, the identification of the substrate access channel for ferrous iron to the active site is important to fully understand this enzymatic system. In fact, whether the iron reaches the active site from the distal or the proximal porphyrin side is still under debate. In this study we have thoroughly addressed this question in <em>Listeria monocytogenes</em> coproporphyrin ferrochelatase by X-ray crystallography, steady-state and pre-steady-state imidazole ligand binding studies, together with a detailed spectroscopic characterization using resonance Raman and UV–vis absorption spectroscopies in solution. Analysis of the X-ray structures of coproporphyrin ferrochelatase-coproporphyrin III crystals soaked with ferrous iron shows that iron is present on both sides of the porphyrin. The kinetic and spectroscopic study of imidazole binding to coproporphyrin ferrochelatase‑iron coproporphyrin III clearly indicates the presence of two possible binding sites in this monomeric enzyme that influence each other, which is confirmed by the observed cooperativity at steady-state and a biphasic behavior in the pre-steady-state experiments. The current results are discussed in the context of the entire heme biosynthetic pathway and pave the way for future studies focusing on protein-protein interactions.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0162013424002058/pdfft?md5=469c947872a1222658468d58e084af00&pid=1-s2.0-S0162013424002058-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987108","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":"Tri-aryl antimony(V) hydroximato and hydroxamato complexes: Combining lipophilic Sb(III/V) and hydroxamic acids in combating Leishmania","authors":"Charles R.M. Soukup,&nbsp;Rebekah N. Duffin,&nbsp;Kirralee J. Burke,&nbsp;Philip C. Andrews","doi":"10.1016/j.jinorgbio.2024.112674","DOIUrl":"10.1016/j.jinorgbio.2024.112674","url":null,"abstract":"<div><p>Six novel tri-aryl antimony(V) hydroximato complexes (<strong>3–8</strong>) with composition [SbAr₃(O₂NCR)] (<strong>3</strong>: Ar = Ph, R = <em>o</em>-(OH)Ph, <strong>4</strong>: Ar = Ph, R = Me, <strong>5</strong>: Ar = Ph, R = Ph; <strong>6</strong>: Ar = Mes, R = Me, <strong>7</strong>: Ar = Mes, R = Ph, <strong>8</strong>: Ar = Mes, R = <em>o</em>-(OH)Ph (where Ph = phenyl, Me = methyl, Mes = mesityl)), were synthesised and evaluated for anti-parasitic activity towards <em>Leishmania major</em> (<em>L. major</em>) promastigotes and amastigotes. Complexes of the form [SbAr₃(O₂NCR)], with the dianionic hydroximato ligand binding <em>O,O′</em>-bidentate to the Sb(V) centre, exist in the solid-state for the mesityl-derived complexes. In contrast, the phenyl-ligated Sb(V) complexes crystallise as the hexacoordinate, hydroxamato species [SbPh₃(O₂NHC(OH))], with the OH ligand derived from entrained H₂O in the crystallisation solvent. It is found that both the aryl and hydroximato ligands are found to influence the bioactivity of the Sb(V) complexes. Complexes <strong>3–8</strong> exhibited varied anti-promastigote activity with IC₅₀ values ranging from 1.53 μM for <strong>6</strong> to 36.0 μM for <strong>3</strong>, also reflected in varied anti-amastigote activity with a percentage infection range of 5.50% for <strong>6</strong> to 29.00% for <strong>3</strong> at a concentration of 10 μM. The complexes were relatively non-toxic to human fibroblasts with an IC₅₀ value range of 59.3 μM (<strong>7</strong>) to ≥100 μM (<strong>3–6</strong>, <strong>8</strong>), and exhibited varied toxicity towards J774.1 A macrophages (IC₅₀: 3.97 (<strong>6</strong>) to ≥100 (<strong>8</strong>) μM). All complexes showed enhanced activity compared to the parent hydroxamic acids.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0162013424001983/pdfft?md5=95fa2fb1ccaca4c5a1d6ff65e05284e1&pid=1-s2.0-S0162013424001983-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141851112","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":"Ga complexes of 8-hydroxyquinoline-2-carboxylic acid: Chemical speciation and biological activity","authors":"Izabela Ryza ,&nbsp;Claudia Granata ,&nbsp;Nadia Ribeiro ,&nbsp;Edyta Nalewajko-Sieliwoniuk ,&nbsp;Andreas Kießling ,&nbsp;Marta Hryniewicka ,&nbsp;Winfried Plass ,&nbsp;Beata Godlewska-Żyłkiewicz ,&nbsp;Sandra Cabo Verde ,&nbsp;Demetrio Milea ,&nbsp;Sofia Gama","doi":"10.1016/j.jinorgbio.2024.112670","DOIUrl":"10.1016/j.jinorgbio.2024.112670","url":null,"abstract":"<div><p>The binding ability of 8-hydroxyquinoline-2-carboxylic acid (8-HQA) towards Ga³⁺ has been investigated by ISE<img>H⁺ (Ion Selective Electrode, glass electrode) potentiometric and UV/Vis spectrophotometric titrations in KCl_(aq) at <em>I</em> = 0.2 mol dm⁻³ and at <em>T</em> = 298.15 K. Further experiments were also performed adopting both the metal (with Fe³⁺ as competing cation) and ligand-competition approaches (with EDTA as competing ligand). Results gave evidence of the formation of the [Ga(8-HQA)]⁺, [Ga(8-HQA)(OH)], [Ga(8-HQA)(OH)₂]⁻ and [Ga(8-HQA)₂]⁻ species, the latter being so far the most stable, as also confirmed by ESI-MS analysis. Experiments were also designed to determine the stability constants of the [Ga(EDTA)]⁻ and [Ga(EDTA)(OH)]²⁻ in the above conditions. Due to the relevance of Ga³⁺ hydrolysis in aqueous systems, literature data on this topic were collected and critically analyzed, providing equations for the calculation of mononuclear Ga³⁺ hydrolysis constants at <em>T</em> = 298.15 K, in different ionic media, in the ionic strength range 0 &lt; <em>I</em> / mol dm⁻³ ≤ 1.0. The synthesis and characterization (by ElectroSpray Ionization – Mass Spectrometry (ESI-MS), Attenuated Total Reflectance - Fourier-Transform Infrared Spectroscopy (ATR-FTIR) and ThermoGravimetric Analysis (TGA)) of Ga³⁺/8-HQA complexes were also performed, identifying [Ga(8-HQA)₂]⁻ as the main isolated species, even in the solid state. Finally, the potential effects of 8-HQA and Ga³⁺/8-HQA complex towards human microbiota exposed to ionizing radiation were evaluated (namely <em>Actinomyces viscosus</em>, <em>Streptococcus mutans</em>, <em>Streptococcus sobrinus</em>, <em>Pseudomonas putida</em>, <em>Pseudomonas fluorescens</em> and <em>Escherichia coli</em>), as well as their anti-proliferative and anti-inflammatory properties. A radioprotective effect of Ga³⁺/8-HQA complex was observed on <em>Actinomyces viscosus</em>, while showing a potential radiosensitizing effect against <em>Streptococcus mutans</em> and <em>Streptococcus sobrinus</em>. No cytotoxicity on RAW264.7 murine macrophage cells was observed, neither for the free ligand or Ga³⁺/8-HQA complex. Nevertheless, Ga³⁺/8-HQA complex highlighted potential anti-inflammatory properties.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0162013424001946/pdfft?md5=8071b26e3edf40d588f6eeed3f706ad6&pid=1-s2.0-S0162013424001946-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786943","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":"Resonance Raman spectral analysis of the heme site structure of cytochrome c oxidase with its positive regulator CHCHD2","authors":"Sachiko Yanagisawa ,&nbsp;Takuto Kamei ,&nbsp;Atsuhiro Shimada ,&nbsp;Stephanie Gladyck ,&nbsp;Siddhesh Aras ,&nbsp;Maik Hüttemann ,&nbsp;Lawrence I. Grossman ,&nbsp;Minoru Kubo","doi":"10.1016/j.jinorgbio.2024.112673","DOIUrl":"10.1016/j.jinorgbio.2024.112673","url":null,"abstract":"<div><p>Cytochrome <em>c</em> oxidase (CcO) reduces O₂, pumps protons in the mitochondrial respiratory chain, and is essential for oxygen consumption in the cell. The coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2; also known as mitochondrial nuclear retrograde regulator 1 [MNRR1], Parkinson's disease 22 [PARK22] and aging-associated gene 10 protein [AAG10]) is a protein that binds to CcO from the intermembrane space and positively regulates the activity of CcO. Despite the importance of CHCHD2 in mitochondrial function, the mechanism of action of CHCHD2 and structural information regarding its binding to CcO remain unknown. Here, we utilized visible resonance Raman spectroscopy to investigate the structural changes around the hemes in CcO in the reduced and CO-bound states upon CHCHD2 binding. We found that CHCHD2 has a significant impact on the structure of CcO in the reduced state. Mapping of the heme peripheries that result in Raman spectral changes in the structure of CcO highlighted helices IX and X near the hemes as sites where CHCHD2 takes action. Part of helix IX is exposed in the intermembrane space, whereas helix X, located between both hemes, may play a key role in proton uptake to a proton-loading site in the reduced state for proton pumping. Taken together, our results suggested that CHCHD2 binds near helix IX and induces a structural change in helix X, accelerating proton uptake.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141853892","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, physicochemical and pharmacological characterizations of a tetra-[methylimidazolium] dihydrogen decavanadate, inhibiting the IGR39 human melanoma cells development","authors":"Taissir Aissa ,&nbsp;Dorra Aissaoui-Zid ,&nbsp;Wassim Moslah ,&nbsp;Oussema Khamessi ,&nbsp;Regaya Ksiksi ,&nbsp;Maike Oltermann ,&nbsp;Michael Ruck ,&nbsp;Mohamed Faouzi Zid ,&nbsp;Najet Srairi-Abid","doi":"10.1016/j.jinorgbio.2024.112672","DOIUrl":"10.1016/j.jinorgbio.2024.112672","url":null,"abstract":"<div><p>Melanoma is a skin cancer that arises from melanocytes and can spread quickly to the other organs of the body, if not treated early. Generally, melanoma shows an inherent resistance to conventional therapies. In this regard, new potential drugs are being developed as possible treatments for melanoma. In this paper, we report the synthesis of a new decavanadate compound with organic molecules for a potential therapeutic application. The tetra-[methylimidazolium] dihydrogen decavanadate(V) salt (C₄H₇N₂)₄[H₂V₁₀O₂₈] is characterized by single-crystal X-ray diffraction, by FT-IR, UV–Vis and ⁵¹V NMR spectroscopy, as well as by thermal analysis (TGA and DSC). The compound crystallizes in the monoclinic centrosymmetric space group <em>P</em>2₁/<em>c</em>. Its formula unit consists of one dihydrogen decavanadate anion [H₂V₁₀O₂₈]⁴⁻ and four organic 4-methylimidazolium cations (C₄H₇N₂)⁺. Important intermolecular interactions are N-H···O and O-H···O hydrogen bonds and π-π stacking interactions between the organic cations, revealed by analysis of the Hirshfeld surface and its two-dimensional fingerprint plots. Interestingly, this compound inhibits the viability of IGR39 cells with IC₅₀ values of 14.65 μM and 4 μM after 24 h and 72 h of treatment, respectively. The analysis of its effect by flow cytometry using an Annexin V-FITC/IP cell labeling, showed that (C₄H₇N₂)₄H₂V₁₀O₂₈ compound induced IGR39 cell apoptosis and necrosis. Molecular docking studies performed against TNFR1 and GPR40, as putative targets, suggest that the (C₄H₇N₂)₄[H₂V₁₀O₂₈] compound may act as inhibitor of these proteins, known to be overexpressed in melanoma cells. Therefore, we could consider it as a new potential metallodrug against melanoma.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141853588","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}