Journal of Inorganic Biochemistry最新文献

{"title":"A thiopyridine-bound mirror-image copper center in an artificial non-heme metalloenzyme","authors":"Yoshitsugu Morita,&nbsp;Hiroki Kubo,&nbsp;Ryusei Matsumoto,&nbsp;Nobutaka Fujieda","doi":"10.1016/j.jinorgbio.2024.112694","DOIUrl":"10.1016/j.jinorgbio.2024.112694","url":null,"abstract":"<div><p>Artificial metalloenzymes, in which a metal complex and protein matrix are combined, have been synthesized to catalyze stereoselective reactions using the chiral environment provided by the protein cavity. Artificial metalloenzymes can be engineered by the chemical modification and mutagenesis of the protein matrix. We developed artificial non-heme metalloenzymes using a cupin superfamily protein (TM1459) with a 4-His tetrad-metal-binding motif. The Cu-bound H52A/C106D mutant with 3-His triad showed a <em>S</em>-enantioselective Michael addition of nitromethane to α,β-unsaturated ketone, 2-aza-chalcone <strong>1</strong>. In this study, we demonstrated a chemical modification near the copper-binding site of this mutant to reverse its enantioselectivity. For chemical modification, the amino acid on the <em>Si</em>-face of the binding state of <strong>1</strong> to the copper center was replaced with Cys, followed by reaction with 4,4′-dithiopyridine (4-PDS) to form <em>S</em>-(pyridin-4-ylthio)cysteine (Cys-4py). Cu-bound I49C-4py/H52A/C106D showed reversal of the enantioselectivity from <em>S</em>-form to <em>R</em>-form (<em>ee</em> = 71%, (<em>R</em>)). The effect of steric hindrance of the amino acids at position 49 on enantioselectivity was investigated using I49X/H52A/C106D mutants (X = A, C, I, F, and W). Additionally, chemical modification with 2,2′-dithiopyridine (2-PDS) produced I49-2py/H52A/C106D, which showed lower <em>R</em>-enantioselectivity than I49-4py/H52A/C106D. Among the mutants, the 4py-modification on the <em>Si</em>-face was the most effective in reversing the enantioselectivity. By tuning the <em>Re-</em>face side, the H54A mutation introduced into the I49C-4py/H52A/C106D increased the <em>R</em>-enantioselectivity (<em>ee</em> = 88%, (<em>R</em>)). X-ray crystallography revealed a coordinated structure with ligation of thiopyridine in Cu-bound I49C-4py/H52A/H54A/C106D.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142011814","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":"Binding of yeast and human cytochrome c to cardiolipin nanodiscs at physiological ionic strength","authors":"Ariel K. Frederick ,&nbsp;Bruce E. Bowler","doi":"10.1016/j.jinorgbio.2024.112699","DOIUrl":"10.1016/j.jinorgbio.2024.112699","url":null,"abstract":"<div><p>Binding of cytochrome <em>c</em> (Cyt<em>c</em>) to membranes containing cardiolipin (CL) is of considerable interest because of the importance of this interaction in the early stages of apoptosis. The molecular-level determinants of this interaction are still not well defined and there appear to be species-specific differences in Cyt<em>c</em> affinity for CL-containing membranes. Many studies are carried out at low ionic strength far from the 100–150 mM ionic strength within mitochondria. Similarly, most binding studies are done at Cyt<em>c</em> concentrations of 10 μM or less, much lower that the estimated range of 0.1 to 5 mM Cyt<em>c</em> present in mitochondria. In this study, we evaluate binding of human and yeast Cyt<em>c</em> to CL nanodiscs using size exclusion chromatography at 25 μM Cyt<em>c</em> concentration and 100 mM ionic strength. We find that yeast Cyt<em>c</em> affinity for CL nanodiscs is much stronger than that of human Cyt<em>c</em>. Mutational analysis of the site A binding surface shows that lysines 86 and 87 are more important for yeast Cyt<em>c</em> binding to CL nanodiscs than lysines 72 and 73, counter to results at lower ionic strength. Analysis of the electrostatic surface potential of human versus yeast Cyt<em>c</em> shows that the positive potential due to lysines 86 and 87 and other nearby lysines (4, 5, 11, 89) is stronger than that due to lysines 72 and 73. In the case of human Cyt<em>c</em> the positive potential around site A is less uniform and likely weakens electrostatic binding to CL membranes through site A.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044570","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":"Ru-terpyridine complexes containing clotrimazole as potent photoactivatable selective antifungal agents","authors":"Carlos Gonzalo-Navarro ,&nbsp;Antonio J. Troyano ,&nbsp;Beatriz García-Béjar Bermejo ,&nbsp;Juan Ángel Organero ,&nbsp;Anna Massaguer ,&nbsp;Lucía Santos ,&nbsp;Ana M. Rodríguez ,&nbsp;Blanca R. Manzano ,&nbsp;Gema Durá","doi":"10.1016/j.jinorgbio.2024.112692","DOIUrl":"10.1016/j.jinorgbio.2024.112692","url":null,"abstract":"<div><p>The overuse of antimicrobial agents in medical and veterinary applications has led to the development of antimicrobial resistance in some microorganisms and this is now one of the major concerns in modern society. In this context, the use of transition metal complexes with photoactivatable properties, which can act as drug delivery systems triggered by light, could become a potent strategy to overcome the problem of resistance. In this work several Ru complexes with terpyridine ligands and the clotrimazole fragment, which is a potent antimycotic drug, were synthesized. The main goal was to explore the potential photoactivated activity of the complexes as antifungal agents and evaluate the effect of introducing different substituents on the terpyridine ligand. The complexes were capable of delivering the clotrimazole unit upon irradiation with visible light in a short period of time. The influence of the substituents on the photodissociation rate was explained by means of TD-DFT calculations. The complexes were tested against three different yeasts, which were selected based on their prevalence in fungal infections. The complex in which a carboxybenzene unit was attached to the terpyridine ligand showed the best activity against the three species under light, with minimal inhibitory concentration values of 0.88 μM and a phototoxicity index of 50 achieved. The activity of this complex was markedly higher than that of free clotrimazole, especially upon irradiation with visible light (141 times higher). The complexes were more active on yeast species than on cancer cell lines.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141991075","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":"Dimolybdenum (II,II) paddlewheel complexes bearing non-steroidal anti-inflammatory drug ligands: Insights into the chemico-physical profile and first biological assessment","authors":"Lorenzo Chiaverini ,&nbsp;Valentina Notarstefano ,&nbsp;Iogann Tolbatov ,&nbsp;Paolo Umari ,&nbsp;Elisabetta Giorgini ,&nbsp;Lidia Ciccone ,&nbsp;Riccardo Di Leo ,&nbsp;Letizia Trincavelli ,&nbsp;Chiara Giacomelli ,&nbsp;Laura Marchetti ,&nbsp;Tiziano Marzo ,&nbsp;Diego La Mendola ,&nbsp;Alessandro Marrone","doi":"10.1016/j.jinorgbio.2024.112697","DOIUrl":"10.1016/j.jinorgbio.2024.112697","url":null,"abstract":"<div><p>Multinuclear complexes are metal compounds featured by adjacent bound metal centers that can lead to unconventional reactivity. Some M₂L₄-type paddlewheel dinuclear complexes with monoanionic bridging ligands feature promising properties, including therapeutic ones. Molybdenum has been studied for the formation of multiple-bonded M²⁺ compounds due to their unique scaffold, redox, and spectroscopic properties as well as for applications in several fields including catalysis and biology. These latter are much less explored and only sporadic studies have been carried out. Here, a series of four dimolybdenum (II,II) carboxylate paddlewheel complexes were synthesized using different Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) as ligands. The reaction of (NH₄)₅[Mo₂Cl₉]·H₂O with the selected NSAIDs in methanol produced the complexes Mo₂(μ-O₂CR)₄ where RCO₂ is ibuprofen (<strong>1</strong>), naproxen (<strong>2</strong>), aspirin (<strong>3</strong>) and indomethacin (<strong>4</strong>). The products were obtained in good yields and extensively characterized with integrated techniques. Stability and solution behaviour were studied using a mixed experimental and computational approach. Finally, the biological activity of <strong>1</strong> and <strong>3</strong> (i.e. the most reactive and the most stable compounds of the series, respectively) was preliminarily assessed confirming the disassembling of the molecules in the biological milieu. Overall, some very interesting results emerged for these unconventional compounds from a mechanistic point of view.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0162013424002216/pdfft?md5=5cebcf4192170962e7d1387edb169d21&pid=1-s2.0-S0162013424002216-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984772","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":"Ciclopirox platinum(IV) conjugates suppress tumors by promoting mitophagy and provoking immune responses","authors":"Suying Li ,&nbsp;Shuaiqi Feng ,&nbsp;Yan Chen ,&nbsp;Bin Sun ,&nbsp;Ning Zhang ,&nbsp;Yanna Zhao ,&nbsp;Jun Han ,&nbsp;Zhifang Liu ,&nbsp;Yan-Qin He ,&nbsp;Qingpeng Wang","doi":"10.1016/j.jinorgbio.2024.112696","DOIUrl":"10.1016/j.jinorgbio.2024.112696","url":null,"abstract":"<div><p>Mitophagy is an important target for antitumor drugs development. A series of ciclopirox (CPX) platinum(IV) hybrids targeting PTEN induced putative kinase 1 (PINK1)/Parkin mediated mitophagy were designed and prepared as antitumor agents. The dual CPX platinum(IV) complex with cisplatin core was screened out as a candidate, which displayed promising antitumor activities both <em>in vitro</em> and <em>in vivo</em>. Mechanistically, it caused serious DNA damage in tumor cells. Then, remarkable mitochondrial damage was induced accompanied by the mitochondrial membrane depolarization and reactive oxygen species generation, which further promoted apoptosis through the Bcl-2/Bax/Caspase3 pathway. Furthermore, mitophagy was ignited <em>via</em> the PINK1/Parkin/P62/LC3 axis, and exhibited positive influence on promoting the apoptosis of tumor cells. The antitumor immunity was boosted by the block of immune check point programmed cell death ligand-1 (PD-L1), which further increased the density of T cells in tumors. Subsequently, the metastasis of tumor cells was inhibited by inhibiting angiogenesis in tumors.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141978509","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":"Endoplasmic reticulum-targeted iridium(III) photosensitizer induces pyroptosis for augmented tumor immunotherapy","authors":"Yun-Shi Zhi ,&nbsp;Tie Chen ,&nbsp;Bin-Fa Liang ,&nbsp;Shan Jiang ,&nbsp;Da-Hong Yao ,&nbsp;Zhen-Dan He ,&nbsp;Chen-Yang Li ,&nbsp;Liang He ,&nbsp;Zheng-Yin Pan","doi":"10.1016/j.jinorgbio.2024.112695","DOIUrl":"10.1016/j.jinorgbio.2024.112695","url":null,"abstract":"<div><p>An ideal tumor treatment strategy involves therapeutic approaches that can enhance the immunogenicity of the tumor microenvironment while simultaneously eliminating the primary tumor. A cholic acid-modified iridium(III) (<strong>Ir3</strong>) photosensitizer, targeted to the endoplasmic reticulum (ER), has been reported to exhibit potent type I and type II photodynamic therapeutic effects against triple-negative breast cancer (MDA-MB-231). This photosensitizer induces pyroptotic cell death mediated by gasdermin E (GSDME) through photodynamic means and enhances tumor immunotherapy. Mechanistic studies have revealed that complex <strong>Ir3</strong> induces characteristics of damage-related molecular patterns (DAMPs) in MDA-MB-231 breast cancer cells under light conditions. These include cell-surface calreticulin (CRT) eversion, extracellular high mobility group box 1 (HMGB1) and ATP release, accompanied by ER stress and increased reactive oxygen species (ROS). Consequently, complex <strong>Ir3</strong> promotes dendritic cell maturation and antigen presentation under light conditions, fully activates T cell-dependent immune response <em>in vivo</em>, and ultimately eliminates distant tumors while destroying primary tumors. In conclusion, immune regulation and targeted intervention mediated by metal complexes represent a new and promising approach to tumor therapy. This provides an effective strategy for the development of combined targeted therapy and immunotherapy.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994987","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":"Organotin(IV) complexes derived from 2,6-diacetylpyridine bis(2-hydroxybenzoylhydrazone) as prospective anti-proliferative agents: Synthesis, characterization, structures and in vitro anticancer activity","authors":"Tushar S. Basu Baul ,&nbsp;Bietlaichhai Hlychho ,&nbsp;Siddhartha Das Pramanik ,&nbsp;Antonin Lyčka ,&nbsp;Partha Roy ,&nbsp;Abdallah G. Mahmoud ,&nbsp;M. Fátima C. Guedes da Silva","doi":"10.1016/j.jinorgbio.2024.112693","DOIUrl":"10.1016/j.jinorgbio.2024.112693","url":null,"abstract":"<div><p>Six organotin(IV) complexes, <em>viz.</em>, [Me₂Sn(L)] (<strong>1</strong>), [<em>n</em>-Bu₂Sn(L)] (<strong>2</strong>), [<em>n</em>-Oct₂Sn(L)] (<strong>3</strong>), [Bz₂Sn(L)]·0.5C₇H₈ (<strong>4</strong>), [<em>n</em>-BuSn(L)Cl] (<strong>5</strong>), and [PhSn(L)Cl] (<strong>6</strong>), were synthesized using a 2,6-diacetylpyridine bis(2-hydroxybenzoylhydrazone), <strong>H</strong>_{<strong>2</strong>}<strong>L</strong>. Compounds were characterized by Fourier transform infrared (FT-IR), High-resolution mass spectrometry (HRMS), and solutions Fourier transform nuclear magnetic resonance (FT-NMR) spectroscopies. The structures <strong>1</strong>–<strong>6</strong> were established by single-crystal X-ray diffraction (SC-XRD) analysis. Diffraction results evidenced that complexes <strong>1–6</strong> were seven-coordinated mononuclear species with the equatorial plane comprising the pentagonal N₃O₂ chelate ring of the doubly deprotonated L and two axial ligands, either R (R = Me, <em>n</em>-Bu, <em>n</em>-Oct, Bz) or R (<em>n</em>-Bu or Ph) and Cl ligands. Additionally, the photophysical properties were examined due to the enhanced conjugation and rigidity of the molecules while thermogravimetric analysis was carried out to evaluate the thermal stabilities of compounds. The anti-proliferative activity of the complexes <strong>1</strong>–<strong>6</strong> was tested against prostate cancer cells (DU-145) and normal human embryonic kidney cells (HEK-293). Among the compounds, dibutyltin compound <strong>2</strong> exhibited increased anti-proliferative activity, with an IC₅₀ value of 6.16 ± 1.56 μM. The investigation of its mechanism of action involves using AO/EB (acridine orange/ethidium bromide) and ROS (reactive oxygen species) generation assays. This likely detects apoptotic morphological alterations in the nucleus of the cells, with ROS generation ultimately leading to apoptosis and cell death. The superior activity of <strong>2</strong> may be attributed to the C···H contacts and respective higher <em>d</em>_<em>e</em> outside and <em>d</em>_<em>i</em> inside distances from the Hirshfeld surface. Thus, these compounds could be a promising alternative to classical chemotherapy agents.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142088001","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":"Kinetic and structural analysis of redox-reversible artificial imine reductases","authors":"Alex H. Miller ,&nbsp;Ingrid B.S. Martins ,&nbsp;Elena V. Blagova ,&nbsp;Keith S. Wilson ,&nbsp;Anne-K. Duhme-Klair","doi":"10.1016/j.jinorgbio.2024.112691","DOIUrl":"10.1016/j.jinorgbio.2024.112691","url":null,"abstract":"<div><p>Three artificial imine reductases, constructed <em>via</em> supramolecular anchoring utilising Fe^III-azotochelin, a natural siderophore, to bind an iridium-containing catalyst to periplasmic siderophore-binding protein (PBP) scaffolds, have previously been synthesised and subjected to catalytic testing. Despite exhibiting high homology and possessing conserved siderophore anchor coordinating residues, the three artificial metalloenzymes (ArMs) displayed significant variability in turnover frequencies (TOFs). To further understand the catalytic properties of these ArMs, their kinetic behaviour was evaluated with respect to the reduction of three cyclic imines: dihydroisoquinoline, harmaline, and papaverine. Kinetic analyses revealed that all examined ArMs adhere to Michaelis-Menten kinetics, with the most pronounced saturation profile observed for the substrate harmaline. Additionally, molecular docking studies suggested varied hydrogen-bonding interactions between substrates and residues within the artificial binding pocket. Pi-stacking and pi-cation interactions were identified for harmaline and papaverine, corroborating the higher affinity of these substrates for the ArMs in comparison to dihydroisoquinoline. Furthermore, it was demonstrated that multiple cavities are capable of accommodating substrates in close proximity to the catalytic centre, thereby rationalising the moderate enantioselectivity conferred by the unmodified scaffolds.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0162013424002150/pdfft?md5=dd1b980382c9c149dbf91f0c6540dbaa&pid=1-s2.0-S0162013424002150-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911135","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":"Synthesis and antitumor activity of copper(II) complexes of imidazole derivatives","authors":"Xiaofang Li ,&nbsp;Kaiyong Chen ,&nbsp;Jilei Lai ,&nbsp;Shanshan Wang ,&nbsp;Yihan Chen ,&nbsp;Xiyu Mo ,&nbsp;Zilu Chen","doi":"10.1016/j.jinorgbio.2024.112690","DOIUrl":"10.1016/j.jinorgbio.2024.112690","url":null,"abstract":"<div><p>Complexes [Cu(PI)₂(H₂O)](NO₃)₂ (<strong>1</strong>), [Cu(PBI)₂(NO₃)]NO₃ (<strong>2</strong>), [Cu(TBI)₂(NO₃)]NO₃ (<strong>3</strong>), [Cu(BBIP)₂](ClO₄)₂ (<strong>4</strong>) and [Cu(BBIP)(CH₃OH)(ClO₄)₂] (<strong>5</strong>) were synthesized from the reactions of Cu(II) salts with 2-(2′-pyridyl)imidazole (PI), (2-(2′-pyridyl)benzimidazole (PBI), 2-(4′-thiazolyl)-benzimidazole (TBI), 2,6-bis(benzimidazol-2-yl)-pyridine (BBIP), respectively. Their compositions and crystal structures were determined. Their in-vitro antitumor activities were screened on four cancer cell lines and one normal cell line (HL-7702) using cisplatin as the positive control. Complexes <strong>2</strong> and <strong>4</strong> show higher cytotoxicity than the other three complexes. The cytotoxicity of complex <strong>2</strong> are comparable to those for cisplatin, and the cytotoxicity for <strong>4</strong> are much higher than those for cisplatin. From a viewpoint of antitumor, <strong>2</strong> might be a nice choice on the tumor cell line of T24 because its IC50 values on T24 and HL-7702 are 15.03 ± 1.10 and 21.34 ± 0.35, respectively. Thus, a mechanistic study for complexes <strong>2</strong> and <strong>4</strong> on T24 cells was conducted. It revealed that they can reduce mitochondrial membrane potential and increase mitochondrial membrane permeability, resulting in increased intracellular ROS levels, Ca²⁺ inward flow, dysfunctional mitochondria and the eventual cell apoptosis. In conclusion, they can induce cell apoptosis through mitochondrial dysfunction. These findings could be useful in the development of new antitumor agents.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911136","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":"Development of novel organometallic sulfonamides with N-ethyl or N-methyl benzenesulfonamide units as potential human carbonic anhydrase I, II, IX and XII isoforms' inhibitors: Synthesis, biological evaluation and docking studies","authors":"Miguel Gallardo ,&nbsp;Rodrigo Arancibia ,&nbsp;Claudiu T. Supuran ,&nbsp;Alessio Nocentini ,&nbsp;David Villaman ,&nbsp;Patricia M. Toro ,&nbsp;Michelle Muñoz-Osses ,&nbsp;Carolina Mascayano","doi":"10.1016/j.jinorgbio.2024.112689","DOIUrl":"10.1016/j.jinorgbio.2024.112689","url":null,"abstract":"<div><p>In the search of new cymantrenyl- and ferrocenyl-sulfonamides as potencial inhibitors of human carbonic anhydrases (hCAs), four compounds based on <em>N</em>-ethyl or <em>N</em>-methyl benzenesulfonamide units have been obtained. These cymantrenyl (<strong>1a-b</strong>) and ferrocenyl (<strong>2a</strong>-<strong>b</strong>) derivatives were prepared by the reaction between aminobenzene sulfonamides ([NH₂-(CH₂)_n-(C₆H₄)-SO₂-NH₂)], where <em>n</em> = 1, 2) with cymantrenyl sulfonyl chloride (<strong>P1</strong>) or ferrocenyl sulfonyl chloride (<strong>P2</strong>), respectively. All compounds were characterized by conventional spectroscopic techniques and cyclic voltammetry. In the solid state, the molecular structures of compounds <strong>1a</strong>, <strong>1b</strong>, and <strong>2b</strong> were determined by single-crystal X–ray diffraction. Biological evaluation as carbonic anhydrases inhibitors were carried out and showed derivatives <strong>1b</strong> y <strong>2b</strong> present a higher inhibition than the drug control for the Human Carbonic Anhydrase (hCA) II and IX isoforms (K_I = 7.3 nM and 5.8 nM, respectively) and behave as selective inhibition for hCA II isoform. Finally, the docking studies confirmed they share the same binding site and interactions as the known inhibitors acetazolamide (AAZ) and agree with biological studies.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911134","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}