JBIC Journal of Biological Inorganic Chemistry最新文献

{"title":"Development and application of metallo-phthalocyanines as potent G-quadruplex DNA binders and photosensitizers","authors":"Ariadna Gil-Martínez,&nbsp;Adrián Hernández,&nbsp;Cristina Galiana-Roselló,&nbsp;Sònia López-Molina,&nbsp;Javier Ortiz,&nbsp;Ángela Sastre-Santos,&nbsp;Enrique García-España,&nbsp;Jorge González-García","doi":"10.1007/s00775-023-02003-3","DOIUrl":"10.1007/s00775-023-02003-3","url":null,"abstract":"<div><p>Metallo-phthalocyanines (<b>MPc</b>) are common photosensitizers with ideal photophysical and photochemical properties. Also, these molecules have shown to interact with non-canonical nucleic acid structures, such as G-quadruplexes, and modulate oncogenic expression in cancer cells. Herein, we report the synthesis and characterisation of two metallo-phthalocyanines containing either zinc (<b>ZnPc</b>) or nickel (<b>NiPc</b>) in the central aromatic core and four alkyl ammonium lateral chains. The interaction of both molecules with G-quadruplex DNA was assessed by UV–Vis, fluorescence and FRET melting experiments. Both molecules bind strongly to G-quadruplexes and stabilise these structures, being <b>NiPc</b> the most notable G-quadruplex stabiliser. In addition, the photosensitizing ability of both metal complexes was explored by the evaluation of the singlet oxygen generation and their photoactivation in cells. Only <b>ZnPc</b> showed a high singlet oxygen generation either by direct observation or by indirect evaluation using a DPBF dye. The cellular evaluation showed mainly cytoplasmic localization of <b>ZnPc</b> and a decrease of the IC₅₀ values of the cell viability of <b>ZnPc</b> upon light activation of two orders of magnitude.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div><div><p>Two metallo-phthalocyanines containing zinc and nickel within the aromatic core have been investigated as G-quadruplex stabilizers and photosensitizers.<b> NiPc</b> shows a high G4 binding but negligible photosensitizing ability while<b> ZnPc</b> exhibits a moderate binding to G-quadruplex together with a high potency to generate singlet oxygen and photocytotoxicity. The interaction with G4s and capacity to be photosensitized is associated with the geometry adopted by the central metal core of the phthalocyanine scaffold.</p></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 5","pages":"495 - 507"},"PeriodicalIF":3.0,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-023-02003-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4574739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of zinc (II) binding and dimeric protein structure of the XIAP-RING domain by copper (I) ions","authors":"Kathryn E. Splan,&nbsp;Sylvia R. Choi,&nbsp;Ruth E. Claycomb,&nbsp;Isaiah K. Eckart-Frank,&nbsp;Shreya Nagdev,&nbsp;Madeline E. Rodemeier","doi":"10.1007/s00775-023-02002-4","DOIUrl":"10.1007/s00775-023-02002-4","url":null,"abstract":"<div><p>Modulation of metalloprotein structure and function via metal ion substitution may constitute a molecular basis for metal ion toxicity and/or metal-mediated functional control. The X-linked Inhibitor of Apoptosis Protein (XIAP) is a metalloprotein that requires zinc for proper structure and function. In addition to its role as a modulator of apoptosis, XIAP has been implicated in copper homeostasis. Given the similar coordination preferences of copper and zinc, investigation of XIAP structure and function upon interaction with copper is relevant. The Really Interesting New Gene (RING) domain of XIAP is representative of a class of zinc finger proteins that utilize a bi-nuclear zinc-binding motif to maintain proper structure and ubiquitin ligase function. Herein, we report the characterization of copper (I) binding to the Zn₂-RING domain of XIAP. Electronic absorption studies that monitor copper–thiolate interactions demonstrate that the RING domain of XIAP binds 5–6 Cu(I) ions and that copper is thermodynamically preferred relative to zinc. Repetition of the experiments in the presence of the Zn(II)-specific dye Mag-Fura2 shows that Cu(I) addition results in Zn(II) ejection from the protein, even in the presence of glutathione. Loss of dimeric structure of the RING domain, which is a requirement for its ubiquitin ligase activity, upon copper substitution at the zinc-binding sites, was readily observed via size exclusion chromatography. These results provide a molecular basis for the modulation of RING function by copper and add to the growing body of literature that describe the impact of Cu(I) on zinc metalloprotein structure and function.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 5","pages":"485 - 494"},"PeriodicalIF":3.0,"publicationDate":"2023-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4089738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transesterification of RNA model induced by novel dinuclear copper (II) complexes with bis-tridentate imidazole derivatives","authors":"Xiuyang Wang,&nbsp;Jun Shu,&nbsp;Tong Ni,&nbsp;Chengxu Xu,&nbsp;Bin Xu,&nbsp;Xiaoqiang Liu,&nbsp;Kaiming Zhang,&nbsp;Weidong Jiang","doi":"10.1007/s00775-023-02000-6","DOIUrl":"10.1007/s00775-023-02000-6","url":null,"abstract":"<div><p>Two novel bis-tridentate imidazole derivatives were conveniently synthesized using a ‘one-pot’ method. Their dinuclear (Cu₂L¹Cl₄, Cu₂L²Cl₄) and mononuclear (CuL¹Cl₂, CuL²Cl₂?H₂O) copper (II) complexes were synthesized to comparably evaluate their reactivities in the hydrolytic cleavage of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) as a classic RNA model. Single crystals of Cu₂L¹Cl₄ and Cu₂L²Cl₄ indicate that both of them are centrosymmetric, and each central copper ion is penta-coordinated. Regarding the transesterification of HPNP, both of dinuclear ones exhibited excess one order of magnitude rate enhancement in contrast with auto-hydrolysis reaction. Under comparable conditions, dinuclear complexes displayed no more than twofold increase in activity over their mononuclear analogues, which verifies the lack of binuclear cooperation effect due to long Cu-to-Cu space.</p><h3>Graphical Abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 5","pages":"473 - 483"},"PeriodicalIF":3.0,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4178746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel water-soluble thiosemicarbazone Schiff base ligand and its complexes as potential anticancer agents and cellular fluorescence imaging","authors":"Sima Feizpour,&nbsp;Seyed Abolfazl Hosseini-Yazdi,&nbsp;Elham Safarzadeh,&nbsp;Behzad Baradaran,&nbsp;Michal Dusek,&nbsp;Morgane Poupon","doi":"10.1007/s00775-023-02001-5","DOIUrl":"10.1007/s00775-023-02001-5","url":null,"abstract":"<div><p>A novel fluorescent ligand (H₂LCl?1.5CH₃OH, <b>1</b>) was synthesized and metal complexes of <b>1</b> with Mn(II), Fe(III), Ni(II), Cu(II), and Zn(II) were obtained as Mn(HL)₂Cl₂ (<b>2</b>), Fe(HL)₂Cl₃?3H₂O (<b>3</b>), Ni(L)(HL)Cl?8H₂O (<b>4</b>), Cu(HL)Cl₂?4H₂O (<b>5</b>), Zn(H₂L)Cl₃ (<b>6</b>), respectively. These compounds were identified by spectroscopic methods, elemental analysis, molar conductivity, and single-crystal X-ray crystallography. According to the crystal structure of <b>4</b> nickel (II), center is surrounded by two ligands in a distorted octahedral geometry. The ligand and its complexes are soluble in water and have excellent stability. In vitro anti-proliferative activity of these compounds was evaluated against human breast adenocarcinoma (MCF-7) and human lipo-sarcoma (SW-872) as cancer cells and human fibroblasts (HFF-2) as normal cells by MTT assay. Interestingly, complex <b>5</b> exhibited excellent activity against both cancer cells with low IC₅₀ value 22.18?±?0.35?μg/mL (35.66?±?0.56?μM) for SW-872 and 79.41?±?3.54?μg/mL (127.6?±?5.69?μM) for MCF-7 among the compounds and in comparison with paclitaxel (PTX) which acts finely. Morphological changes were evaluated by flow cytometry that revealed apoptosis is the main cause of cell death. Likewise, cell cycle studies indicated the cell cycle arrest in the G₁ and S phases for complex <b>5</b> against MCF-7 and SW-872 cancer cells, while complex <b>6</b> could arrest the MCF-7 and SW-872 cells in G₂ and G₁ phases, respectively. All of the compounds are fluorescent which enabled us to monitor the uptake and intracellular distribution in living human cancer cells by fluorescence microscopy.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 5","pages":"457 - 472"},"PeriodicalIF":3.0,"publicationDate":"2023-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4097814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, characterization, anticancer efficacy evaluation of ruthenium(II) and iridium(III) polypyridyl complexes toward A549 cells","authors":"Lijuan Liang,&nbsp;Yan Yang,&nbsp;Haimei Liu,&nbsp;Fang Yuan,&nbsp;Yuhan Yuan,&nbsp;Wenlong Li,&nbsp;Chunxia Huang,&nbsp;Jing Chen,&nbsp;Yunjun Liu","doi":"10.1007/s00775-023-01997-0","DOIUrl":"10.1007/s00775-023-01997-0","url":null,"abstract":"<div><p>A new ligand DFIP (2-(dibenzo[b,d]furan-3-yl)-1<i>H</i>-imidazo[4,5-f][1,10]phenanthroline) and its two complexes iridium(III) [Ir(ppy)₂(DFIP)](PF₆) (ppy = 2-phenylpyridine, <b>Ir1</b>) and ruthenium(II) [Ru(bpy)₂(DFIP)](PF₆)₂ (bpy = 2,2′-bipyridine, <b>Ru1</b>) were synthesized and characterized. The anticancer effects of the two complexes on A549, BEL-7402, HepG2, SGC-7901, HCT116 and normal LO2 cells were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Complex <b>Ir1</b> shows high cytotoxic activity on A549, BEL-7402, SGC-7901 and HepG2, <b>Ru1</b> exhibits moderate anticancer activity toward A549, BEL-7402 and SGC-7901 cells. The IC₅₀ values of <b>Ir1</b> and <b>Ru1</b> toward A549 are 7.2 ± 0.1 and 22.6 ± 1.4 μM, respectively. The localization of complexes <b>Ir1</b> and <b>Ru1</b> in the mitochondrial, intracellular accumulation of reactive oxygen species (ROS) levels, and the changes of mitochondrial membrane potential (MMP) and cytochrome c (cyto<i>-</i>c) were investigated. Apoptosis and cell cycle were detected by flow cytometry. Immunogenic cell death (ICD) was used to detect the effects of <b>Ir1</b> and <b>Ru1</b> on the A549 using a confocal laser scanning microscope. The expression of apoptosis-related proteins was detected by western blotting. <b>Ir1</b> and <b>Ru1</b> can increase the intracellular ROS levels and release cyto-c, reduce the MMP, leading to the apoptosis of A549 cells and blocking the A549 cells at the G0/G1 phase. Additionally, the complexes caused a decrease of the expression of polyADP-ribose polymerase (PARP), caspase 3, Bcl-2 (B-cell lymphoma-2), PI3K (phosphoinositide-3 kinase) and upregulated the expression of Bax. All these findings indicated that the complexes exert anticancer efficacy to induce cell death through immunogenic cell death, apoptosis, and autophagy.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 4","pages":"421 - 437"},"PeriodicalIF":3.0,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4961873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial and anti-biofilm activity of silver nanoparticles biosynthesized with Cystoseira algae extracts","authors":"Mário Fernandes,&nbsp;Noelia González-Ballesteros,&nbsp;André da Costa,&nbsp;Raúl Machado,&nbsp;Andreia C. Gomes,&nbsp;Maria Carmen Rodríguez-Argüelles","doi":"10.1007/s00775-023-01999-y","DOIUrl":"10.1007/s00775-023-01999-y","url":null,"abstract":"<div><p>Antimicrobial resistance is an ever-growing global concern to public health with no clear or immediate solution. Silver nanoparticles (AgNPs) have long been proposed as efficient agents to fight the growing number of antibiotic-resistant strains. However, the synthesis of these particles is often linked to high costs and the use of toxic, hazardous chemicals, with environmental and health impact. In this study, we successfully produced AgNPs by green synthesis with the aid of the extract of two brown algae—<i>Cystoseira baccata</i> (CB) and <i>Cystoseira tamariscifolia</i> (CT)—and characterized their physico-chemical properties. The NPs produced in both cases (Ag@CB and Ag@CT) present similar sizes, with mean diameters of around 22?nm. The antioxidant activity of the extracts and the NPs was evaluated, with the extracts showing important antioxidant activity. The bacteriostatic and bactericidal properties of both Ag@CB and Ag@CT were tested and compared with gold NPs produced in the same algae extracts as previously reported. AgNPs demonstrated the strongest bacteriostatic and bactericidal properties, at concentrations as low as 2.16?μg/mL against <i>Pseudomonas aeruginosa</i> and <i>Escherichia coli</i>. Finally, the capacity of these samples to prevent the formation of biofilms characteristic of infections with a poorer outcome was assessed, obtaining similar results. This work points towards an alternative for the treatment of bacterial infections, even biofilm-inducing, with the possibility of minimizing the risk of drug resistance, albeit the necessary caution implied using metallic NPs.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 4","pages":"439 - 450"},"PeriodicalIF":3.0,"publicationDate":"2023-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-023-01999-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4812594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steric hindrance, ligand ejection and associated photocytotoxic properties of ruthenium(II) polypyridyl complexes","authors":"Piedad Herrera-Ramírez,&nbsp;Sarah Alina Berger,&nbsp;Dana Josa,&nbsp;David Aguilà,&nbsp;Ana B. Caballero,&nbsp;Pere Fontova,&nbsp;Vanessa Soto-Cerrato,&nbsp;Manuel Martínez,&nbsp;Patrick Gamez","doi":"10.1007/s00775-023-01998-z","DOIUrl":"10.1007/s00775-023-01998-z","url":null,"abstract":"<div><p>Two ruthenium(II) polypyridyl complexes were prepared with the {Ru(phen)₂}²⁺ moiety and a third sterically non-hindering bidentate ligand, namely 2,2′-dipyridylamine (dpa) and <i>N</i>-benzyl-2,2′-dipyridylamine (Bndpa). Hence, complexes [Ru(phen)₂(dpa)](PF₆)₂ (<b>1</b>) and [Ru(phen)₂(Bndpa)](PF₆)₂ (<b>2</b>) were characterized and their photochemical behaviour in solution (acetonitrile and water) was subsequently investigated. Compounds <b>1</b> and <b>2</b>, which do not exhibit notably distorted octahedral coordination environments, contrarily to the homoleptic “parent” compound [Ru(phen)₃](PF₆)₂, experience two-step photoejection of the dpa and Bndpa ligand upon irradiation (1050–430?nm) for several hours. DNA-binding studies revealed that compounds <b>1</b> and <b>2</b> affect the biomolecule differently upon irradiation; while <b>2</b> solely modifies its electrophoretic mobility, complex <b>1</b> is also capable of cleaving it. In vitro cytotoxicity studies with two cancer-cell lines, namely A549 (lung adenocarcinoma) and A375 (melanoma), showed that both <b>1</b> and <b>2</b> are not toxic in the dark, while only <b>1</b> is significantly cytotoxic if irradiated, <b>2</b> remaining non-toxic under these conditions.</p><h3>Graphical abstract</h3><p>Light irradiation of the complex cation [Ru(phen)₂(dpa)]²⁺ leads to the generation of transient Ru species that is present in the solution medium for several hours, and that is significantly cytotoxic, ultimately producing non-toxic free dpa and [Ru(phen)(OH₂)₂]²⁺.</p>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 4","pages":"403 - 420"},"PeriodicalIF":3.0,"publicationDate":"2023-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-023-01998-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4597313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-efficiency oxygen evolution by photosystem II oxygen-evolving complex containing 3Mn per reaction center","authors":"Boris К. Semin,&nbsp;Lira N. Davletshina","doi":"10.1007/s00775-023-01987-2","DOIUrl":"10.1007/s00775-023-01987-2","url":null,"abstract":"<div><p>Ca-depleted photosystem II membranes obtained by treatment with acidic buffer do not contain Ca²⁺ in the Mn₄CaO₅ cluster but contain all extrinsic proteins protecting this cluster (PSII(-Ca/low pH)). However, unlike native photosystem II, Mn cluster in PSII(-Ca/low pH) samples is available for small-sized reductants. Using this property, we investigated the substitution possibility of Mn cation(s) with Fe cation(s) to obtain a chimeric cluster in PSII(-Ca/low pH) samples containing extrinsic proteins. We found that Fe(II) cation replaces Mn cation at pH 6.5, however, PSII(-Ca/low pH) membranes with the 3Mn1Fe chimeric cluster in the oxygen-evolving complex evolve O₂ with high intensity in the presence of exogenous Ca²⁺. The O₂ evolution rate is about 80% of the same rate in PSII(-Ca/low pH) membranes.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 4","pages":"393 - 401"},"PeriodicalIF":3.0,"publicationDate":"2023-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4484863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomimetic synthesis of hydroxytyrosol from conversion of tyrosol by mimicking tyrosine hydroxylase","authors":"Chan Chen,&nbsp;Weikang Tang,&nbsp;Qinfei Chen,&nbsp;Mengqi Han,&nbsp;Qi Shang,&nbsp;Wenbin Liu","doi":"10.1007/s00775-023-01996-1","DOIUrl":"10.1007/s00775-023-01996-1","url":null,"abstract":"<div><p>Hydroxytyrosol, one of the most powerful natural antioxidants, exhibits certificated benefits for human health. In this study, a biomimetic approach to synthesize hydroxytyrosol from the hydroxylation of tyrosol was established. EDTA-Fe²⁺ coordination complex served as an active center to simulate tyrosine hydroxylase. H₂O₂ and ascorbic acid were used as oxygen donor and hydrogen donor, respectively. Hydroxy radical and singlet oxygen contributed to active species. The biomimetic system displayed analogous component, structure, and activity with TyrH. Hydroxytyrosol titer of 21.59?mM, and productivity of 9985.92?mg·L^?1·h^?1 was achieved with 100?mM tyrosol as substrate. The proposed approach provided efficient and convenient route to quickly produce high amount of hydroxytyrosol.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 4","pages":"379 - 391"},"PeriodicalIF":3.0,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-023-01996-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4194932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting cancer lactate metabolism with synergistic combinations of synthetic catalysts and monocarboxylate transporter inhibitors","authors":"Hannah E. Bridgewater,&nbsp;Elizabeth M. Bolitho,&nbsp;Isolda Romero-Canelón,&nbsp;Peter J. Sadler,&nbsp;James P. C. Coverdale","doi":"10.1007/s00775-023-01994-3","DOIUrl":"10.1007/s00775-023-01994-3","url":null,"abstract":"<div><p>Synthetic anticancer catalysts offer potential for low-dose therapy and the targeting of biochemical pathways in novel ways. Chiral organo-osmium complexes, for example, can catalyse the asymmetric transfer hydrogenation of pyruvate, a key substrate for energy generation, in cells. However, small-molecule synthetic catalysts are readily poisoned and there is a need to optimise their activity before this occurs, or to avoid this occurring. We show that the activity of the synthetic organometallic redox catalyst [Os(<i>p</i>-cymene)(TsDPEN)] (<b>1</b>), which can reduce pyruvate to un-natural <span>d</span>-lactate in MCF7 breast cancer cells using formate as a hydride source, is significantly increased in combination with the monocarboxylate transporter (MCT) inhibitor AZD3965. AZD3965, a drug currently in clinical trials, also significantly lowers the intracellular level of glutathione and increases mitochondrial metabolism. These synergistic mechanisms of reductive stress induced by <b>1</b>, blockade of lactate efflux, and oxidative stress induced by AZD3965 provide a strategy for low-dose combination therapy with novel mechanisms of action.\u0000</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 3","pages":"345 - 353"},"PeriodicalIF":3.0,"publicationDate":"2023-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-023-01994-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4353750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}