Journal of Inorganic Biochemistry最新文献

{"title":"Aromatic amino acid based Schiff base copper(II) complexes as potential lung cancer therapeutics: Biological and antioxidant activity, DNA/BSA interaction, mesogenic properties, molecular docking and DFT study","authors":"Hunshisha Pyngrope ,&nbsp;Jagritima Chetia ,&nbsp;Bandashisha Kharpan ,&nbsp;Snehashish Modak ,&nbsp;Tamanna Aktar ,&nbsp;Amit Kumar Pradhan ,&nbsp;Akhilesh Jaiswar ,&nbsp;Pradip C. Paul ,&nbsp;Debasish Maiti","doi":"10.1016/j.jinorgbio.2025.113187","DOIUrl":"10.1016/j.jinorgbio.2025.113187","url":null,"abstract":"<div><div>Three new copper(II) complexes, Cu(L¹)₂, Cu(L²)₂, and Cu(L³)₂, derived from aromatic amino acid based Schiff base ligands, potassium (E)-2-((4-hexadecyloxy)-2-hydroxybenzylidene)amino)-3-phenylpropanoate (HL¹), potassium (E)-2-((4-hexadecyloxy)-2-hydroxybenzylidene)amino)-3-(4-hydroxyphenyl) propanoate (HL²) and potassium (E)-2-((4-hexadecyloxy)-2-hydroxybenzylidene)amino)-3-(1H-indol-2-yl)propanoate (HL³) were synthesized and characterized by using elemental analysis and the spectroscopic techniques viz., UV–visible, ¹³C NMR, ¹H NMR, FT-IR spectroscopy. All three complexes interact effectively with calf thymus-deoxyribonucleic acid (CT-DNA) and Bovine serum albumin (BSA), as evidenced from spectroscopic studies. Among them, Cu(L³)₂ exhibited the strongest biomolecular binding affinity, highest cytotoxic activity against lung adenocarcinoma (A-549) cells, and superior antioxidant capacity in the DPPH (2,2-diphenyl-1-picryhydrazyl) assay. Molecular docking simulations were carried out to evaluate the binding affinity and interaction profiles of aromatic amino acid-based Schiff base Cu(II) complexes with Human Serum Albumin (HSA). The results revealed selective binding at Sudlow's site I, with the binding of Cu(L³)₂ with HSA exhibiting the highest affinity (−5.81 kcal mol⁻¹). The parent ligands HL¹, HL² and HL³ exhibit blue photoluminescence, and the presence of their long alkyl chain substituents induced mesomorphic behaviour with distinct nematic, smectic C, and mosaic textures, respectively. Density functional theory (DFT) calculations supported the experimental findings, revealing optimized geometries and HOMO–LUMO band gaps consistent with their reactivity trends. On the whole, Cu(L³)₂ emerges as the most promising candidate for biomedical applications, while the ligands themselves show potential for functional mesogenic material.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113187"},"PeriodicalIF":3.2,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773238","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":"Special issue on “Metal complexes targeting non-canonical nucleic acid structures”","authors":"Riccardo Bonsignore,&nbsp;Alessio Terenzi","doi":"10.1016/j.jinorgbio.2025.113186","DOIUrl":"10.1016/j.jinorgbio.2025.113186","url":null,"abstract":"","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113186"},"PeriodicalIF":3.2,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888402","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":"Differences in functional cross-talk between loops C and D in two mitochondrial cytochromes","authors":"Dong-Woo Shin ,&nbsp;Fangfang Zhong,&nbsp;Ekaterina V. Pletneva","doi":"10.1016/j.jinorgbio.2025.113182","DOIUrl":"10.1016/j.jinorgbio.2025.113182","url":null,"abstract":"<div><div>The heme in the protein cytochrome (cyt) <em>c</em> is surrounded by loops C and D that differ in their sequences across species. Mutations G41S and Y48H in human (hu) cyt <em>c</em> are associated with thrombocytopenia and have been extensively studied. Herein, we describe effects of the same mutations in horse heart (hh) cyt <em>c</em> and make comparisons to those in the hu protein. While wild-type (WT) hu and hh cyt <em>c</em> proteins have similar global stabilities, unfolding of the hh protein is less cooperative. The differences are further amplified in the mutants. Loop dynamics were probed computationally through MD simulations and experimentally by characterizing the alkaline transition. With G41S and Y48H mutations in hh cyt <em>c</em>, loop C made fewer contacts with loop D and the dynamics of loop D were enhanced. Only the Y48H mutation decreased the reduction potential in hh cyt <em>c</em>, but both G41S and Y48H mutations increased the intrinsic peroxidase activity. The rate constant <em>k</em>_f for the Met-to-Lys ligand switch in the alkaline transition differed in the hu and hh cyt <em>c</em> mutational series: this rate constant decreased upon mutations in the hu protein but increased with analogous mutations in the hh protein. The observed trends are rationalized based on the sequence variation in the two proteins, particularly the identity of residue 46 and differences in interactions it makes with loop D. Functional implications of the sequence difference for electron transfer and peroxidase activity are discussed.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113182"},"PeriodicalIF":3.2,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779744","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":"Unveiling the regio- and stereo-selectivity in situ primary amination of allylic and benzylic C(sp3)–H bonds: The pivotal role of structural evaluation","authors":"Yang Zeng ,&nbsp;Xue Jiang ,&nbsp;Yuxin Shi ,&nbsp;Yujun Si ,&nbsp;Lijun Yang","doi":"10.1016/j.jinorgbio.2025.113184","DOIUrl":"10.1016/j.jinorgbio.2025.113184","url":null,"abstract":"<div><div>Directed evolution of heme enzymes for the catalytic construction of benzylic C(sp³)–N bonds has attracted extensive attention. However, achieving regio- and stereoselective control in the enzyme-catalyzed C(sp³)–H activation step has remained a significant challenge. In this study, the potential energy surface defined by the transition state (TS) can appropriately illustrate the selective amination of C(sp³) − H at allylic or benzylic positions in certain reactive substrates, such as 1-phenyl-1-cyclohexene (<strong>a</strong>). However, this approach is not applicable to certain unreactive substrates, such as allylbenzene (<strong>l</strong>). A comprehensive understanding of the entire process requires methods capable of addressing highly multidimensional problems. Analysis of structural consistency suggested that, when both the attacking distance and angle are taken into account in the molecular dynamics (MD) simulation snapshots, conformations resembling the TS facilitate efficient hydrogen atom abstraction and site-selective enzymatic amination at the predicted positions. In contrast, the unreactive substrate rarely achieves a productive geometry conducive to C − H bond abstraction. Overall, these results highlight the selectivity that can arise due to the distinct geometrical requirements for efficient allylic or benzylic C − H bond amination mediated by cytochrome P450 enzymes.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113184"},"PeriodicalIF":3.2,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733820","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":"On the structural, photophysical and antimicrobial properties of bimetallic Re-Fe coordination compounds bearing diimines ligands","authors":"Emilia R. Serrano ,&nbsp;Pedro M. David Gara ,&nbsp;Juan J. Martínez Medina ,&nbsp;Filippo Prencipe ,&nbsp;Oscar E. Piro ,&nbsp;Gustavo A. Echeverría ,&nbsp;Gabriela Petroselli ,&nbsp;Tatiana Da Ros ,&nbsp;Gustavo T. Ruiz","doi":"10.1016/j.jinorgbio.2025.113178","DOIUrl":"10.1016/j.jinorgbio.2025.113178","url":null,"abstract":"<div><div>A new complex <em>fac</em>-[(ferroceneCO₂)Re^I(CO)₃(dppz)] (dppz = dipyrido[3,2-a:2′,3′-c]phenazine) was obtained and fully characterized by elemental analysis, ¹H and ¹³C NMR, ESI-mass, IR and UV–vis spectroscopy. We also report new insights into the structural and photophysical properties of the <em>fac</em>-[(ferroceneCO₂)Re^I(CO)₃L], where L = 2,2′-bipyridine (bpy) or 1,10-phenanthroline (phen), parent complexes. For all complexes, our results showed that: (i) no singlet oxygen generation was detected in acetonitrile solutions and (ii) they exhibited a very low luminescence quantum yield. However, photoacoustic measurements showed that under photoexcitation the complexes released all the absorbed energy to the medium as prompt heat. The antimicrobial activity of the ferroceneCO₂-Re(CO)₃(phen) complex was detected against both bacteria from American Type Culture Collections (ATCC) and clinically isolated bacterial strains. Antibacterial activity was rationalized in relation to extension of the π-system of the diamine ligands. Additionally, the ferroceneCO₂-Re(CO)₃(phen) complex showed no mutagenic potential.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113178"},"PeriodicalIF":3.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733863","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":"Triple-action Pt(IV) prodrugs of cisplatin and oxaliplatin with indole propionate and 4-phenylbutyrate ligands as potent anticancer agents","authors":"Leila Tabrizi ,&nbsp;Alan M. Jones ,&nbsp;Isolda Romero-Canelon ,&nbsp;Andrea Erxleben","doi":"10.1016/j.jinorgbio.2025.113183","DOIUrl":"10.1016/j.jinorgbio.2025.113183","url":null,"abstract":"<div><div>The synthesis and biological activity of two new platinum(IV) derivatives of cisplatin and oxaliplatin with indole-3-propionate (IPA) and the histone deacetylase inhibitor 4-phenylbutyrate (PBA) in axial position are reported. <em>Cis,cis,trans</em>-[Pt(NH₃)₂Cl₂(IPA)(PBA)] (<strong>1</strong>) and <em>tran</em>s-[Pt(DACH)(OX)(IPA)(PBA)] (<strong>2</strong>) (DACH = (1<em>R</em>,2<em>R</em>)-1,2-cyclohexanediamine; OX = oxalate) were characterized by elemental analysis, ESI-MS, FT-IR, and ¹H, ¹³C{¹H}, and ¹⁹⁵Pt{¹H} NMR spectroscopy. The cytotoxicity of the Pt(IV) complexes was evaluated in A2780 ovarian, A549 lung, PEA1 ovarian, SKOV3 ovarian, PC3 prostate and HCT116 colon cancer cells. Complex <strong>2</strong> is about 100 times more potent than cisplatin and about 30 times more potent than oxaliplatin in HCT116 cells. In contrast to cisplatin and oxaliplatin, <strong>1</strong> and <strong>2</strong> maintain their activity in HCT116 p53-knockout cells. Mechanistic studies indicated a multifactorial mechanism that includes histone deacetylase inhibition, the generation of reactive oxygen species and the disruption of mitochondrial function. The complexes affect the cell cycle and induce apoptotic cell death.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113183"},"PeriodicalIF":3.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733866","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":"NMR investigation on the non-enzymatic breakdown of the glucosinolate sinigrin and its acetylated derivative by copper ions","authors":"Laurenzo D.V. Alba ,&nbsp;Tsubasa Hatanaka ,&nbsp;Tatsuo Yajima ,&nbsp;Shigenobu Yano ,&nbsp;Yasuhiro Funahashi","doi":"10.1016/j.jinorgbio.2025.113181","DOIUrl":"10.1016/j.jinorgbio.2025.113181","url":null,"abstract":"<div><div>Copper is an essential trace element present in many organisms, and the maintenance of its homeostasis is involved in the prevention of diseases, including cancer. Glucosinolates are sulfur-containing glycosides mainly found in cruciferous plants, and are hydrolyzed by the myrosinase enzyme to bioactive compounds such as isothiocyanates that contribute to plant defense against herbivores and exhibit various health-promoting effects in humans. The interaction between Cu and glucosinolates, however, is largely uncharacterized. In this ¹H nuclear magnetic resonance (NMR)-based study, we demonstrated that the glucosinolate sinigrin or its <em>O</em>-acetylated derivative can readily react with Cu(I) ions in solution without the presence of the plant myrosinase enzyme, although Cu(II) ions were found to be unreactive. In aqueous solution, the Cu(I) ions interact with the vinyl group of sinigrin as shown by ¹H NMR spectroscopy. The glycosidic C<img>S bond of sinigrin is eventually cleaved, resulting in the formation of 2-butenenitrile. The reaction can also occur in the presence of Cu(II) and ascorbic acid generating Cu(I) in situ. When the reaction is conducted without triflate in organic solvent, Cu(I) ions were also demonstrated to be able to desulfate <em>O</em>-acetylated sinigrin without cleavage of the glycosidic C<img>S bond. Our findings indicate that Cu(I)-mediated non-enzymatic cleavage plays a key role in the fate of dietary glucosinolates and suggest that these compounds and their hydrolysis products may help sequester excess copper. This study will be developed for other glucosinolates with additional spectroscopic, chromatographic, and analytical methods for further understanding.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113181"},"PeriodicalIF":3.2,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733819","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, and anticancer activity of acylthiourea-ruthenium(II) p-cymene complexes","authors":"Raúl Ramos ,&nbsp;Ana María Plutín ,&nbsp;Raúl Oscar Mocelo ,&nbsp;Jean-Pierre DJukic ,&nbsp;Camila Batista Pinto ,&nbsp;Eduardo E. Castellano ,&nbsp;Gustavo A. Echeverría ,&nbsp;Oscar E. Piro ,&nbsp;Mauricio F. Erben ,&nbsp;Legna Colina-Vegas ,&nbsp;Beatriz N. Cunha ,&nbsp;Alzir A. Batista","doi":"10.1016/j.jinorgbio.2025.113180","DOIUrl":"10.1016/j.jinorgbio.2025.113180","url":null,"abstract":"<div><div>In this work, we report the synthesis and characterization of three novel ruthenium(II) <em>p</em>-cymene complexes coordinated with acylthiourea ligands (<strong>L1−L3</strong>), of general formula [Ru(η⁶-<em>p</em>-cymene)(PPh₃)(<strong>L1–L3</strong>)Cl]PF₆ (<strong>1–3</strong>). Single-crystal X-ray crystallography of the free ligands and their complexes [Ru(η⁶-<em>p</em>-cymene)(PPh₃) (κ¹-S)-(<em>N</em>-benzoyl-<em>N</em>´-cyclopropylthiourea)Cl]PF₆ (<strong>1</strong>), Ru(η⁶-<em>p</em>-cymene)(PPh₃) (κ¹-S)<em>-(N</em>-2-furoyl-<em>N</em>´-cyclopropylthiourea)Cl]PF₆ (<strong>2</strong>), [Ru(η⁶-<em>p</em>-cymene)(PPh₃)] (κ¹-S)-(<em>N</em>-thiophene-2-carbonyl-<em>N</em>´-cyclopropyl thiourea)Cl]PF₆ (<strong>3</strong>) revealed that the acylthiourea ligands act as neutral monodentate donors, coordinating through the sulfur atom (κ¹-S). Application of the Extended Transition State–Natural Orbitals for Chemical Valence method demonstrated that the dominant interaction in complexes <strong>1–3</strong> originates from the overlap between the sulfur lone pair of the ligands and a Ru <em>d</em>-orbital, which plays a decisive role in their stability. The Interacting Quantum Atom analysis showed that both the free and coordinated acylthiourea ligands stabilize their structure through an intramolecular N–H···O=C hydrogen bond. The cytotoxicity of complexes <strong>1–3</strong> was evaluated against the A549 (lung) and MDA-MB-231 (breast) human cancer cell lines. To assess their selectivity, the compounds were also tested against two non-cancerous cell models: MRC-5 (lung fibroblasts) and MCF-10 A (breast epithelial cells). The study revealed high cytotoxicity against the MDA-MB-231 cell line, with IC₅₀ values of 0.62 ± 0.05 μM (<strong>1</strong>), 0.66 ± 0.12 μM (<strong>2</strong>), and 0.53 ± 0.12 μM (<strong>3</strong>). Activity against the A549 cell line was also significant, with IC₅₀ values of 1.05 ± 0.11 μM (<strong>1</strong>), 2.60 ± 0.25 μM (<strong>2</strong>), and 1.04 ± 0.21 μM (<strong>3</strong>). The combination of phosphine and acylthiourea ligands appears critical for achieving high cytotoxic activity.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113180"},"PeriodicalIF":3.2,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712838","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":"Exceptional stability of a Gd-free extracellular fluid MRI contrast agent based on manganese porphyrin","authors":"Keith Tang ,&nbsp;Henry Tieu ,&nbsp;Hanlin Liu ,&nbsp;Naixin Zhao ,&nbsp;Xiao-An Zhang","doi":"10.1016/j.jinorgbio.2025.113175","DOIUrl":"10.1016/j.jinorgbio.2025.113175","url":null,"abstract":"<div><div>Metal-ligand stability plays a central role in medicinal bioinorganic chemistry, as it impacts not only the efficacy but also the safety profiles of metal-based therapeutic and diagnostic agents. Gadolinium-based contrast agents (GBCAs) have been widely applied in clinical magnetic resonance imaging (MRI) scans for decades to enhance the detection of otherwise hardly visible diseases. However, evidence of metal dissociation from Gd chelates <em>in vivo</em> have raised safety concerns and led to the withdrawals of several clinically approved GBCAs in recent years. Here we report an exceptionally high stability of Mn(III)tetracarboxylporphyrin (MnTCP), a Gd-free extracellular fluid CA with high MRI contrast enhancement efficiency at clinic magnetic fields. The stability of MnTCP was systematically investigated under challenging conditions known to cause metal dissociation or transmetallation of GBCAs, as well as most other chelated metal complexes. The kinetic inertness of MnTCP was demonstrated at low pH and high temperature, and no sign of metal dissociation was observed. Incubation of MnTCP with excess of various endogenous metal ions, as well as metal chelators also did not cause any observable transmetalation under neutral or acidic conditions up to 50 days. Moreover, MnTCP is highly stable against reduction by endogenous species, preventing the formation of labile Mn(II)-complex. These findings are consistent with <em>in vivo</em> and intracellular behaviors of MnTCP observed in previous studies. The abnormally high stability of this tetradentate coordination complex can be attributed to structural rigidity, aromaticity and strong metal-ligand orbital interactions.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113175"},"PeriodicalIF":3.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733865","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":"A cyclometalated iridium(III) complex with 2-acetylpyridine-N(4)-ortho-chlorophenyl thiosemicarbazone: Potent antiproliferative and antibacterial activities","authors":"Bruna V. Paes ,&nbsp;Davi N. Costa ,&nbsp;Igor V. Esarev ,&nbsp;Susanne Boschuk ,&nbsp;Petra Lippmann ,&nbsp;Sarah Sant'Anna Maranhão ,&nbsp;Claudia Pessoa ,&nbsp;Ingo Ott ,&nbsp;Heloisa Beraldo","doi":"10.1016/j.jinorgbio.2025.113179","DOIUrl":"10.1016/j.jinorgbio.2025.113179","url":null,"abstract":"<div><div>The cyclometalated [Ir(C<img>N)₂(H2Ac4<em>o</em>ClPh)]Cl·2H₂O complex, hereafter named <strong>Ir(III) complex</strong>, was obtained from the reaction of dichlorotetrakis(2-(2-pyridinyl)phenyl)diiridium(III), [Ir₂(N<img>C)₄Cl₂] (<strong>P1</strong>) with 2-acetylpyridine <em>N</em>(4)-ortho-chlorophenyl thiosemicarbazone (H2Ac4<em>o</em>ClPh). The <strong>Ir(III) complex</strong> and H2Ac4<em>o</em>ClPh exhibited cytotoxic effects against A549 lung and PC3 prostate cancer cells, with IC₅₀ values below 5 μM. Although the <strong>Ir(III) complex</strong> showed a higher IC₅₀ value against PC3 prostate cancer cells than H2Ac4<em>o</em>ClPh, it exhibited a higher selectivity index (SI = IC_{50 L929}/IC_{50 PC3} L929: non-malignant fibroblast cells). The <strong>Ir(III) complex</strong> did not strongly inhibit thioredoxin reductase (TrxR) activity, suggesting that its mode of action does not involve TrxR inhibition. Hoechst 33342 staining revealed that A549 cells treated with the <strong>Ir(III) complex</strong> underwent nuclear fragmentation and chromatin condensation, indicating the occurrence of cell death. After 6 h treatment with <strong>Ir(III) complex</strong>, the iridium levels in A549 tumor cells were almost 75-fold higher than after treatment with the synthesis precursor <strong>P1</strong>, which probably could explain the potent cytotoxic effects of <strong>Ir(III) complex</strong> and the low activity of <strong>P1</strong>. The antibacterial activity of <strong>Ir(III) complex</strong> against <em>Gram</em>-positive <em>Bacillus subtillis</em> bacteria was comparable to that of ciprofloxacin used as a control. The results of the present work represent a significant contribution to the investigations on the pharmacological profile of iridium(III) complexes.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113179"},"PeriodicalIF":3.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733823","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}