Reactive Oxygen Species Inducing Triazolylpyridine-Based Ru(II)/Ir(III) Complexes for Therapeutically Enhanced Triple-Negative Breast Cancer Treatment

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

The effectiveness of existing systemic and targeted therapies remains limited in triple-negative breast cancer (TNBC) treatment. Much research has been conducted on reactive oxygen species (ROS)-mediated cell death to overcome the shortcomings currently applied chemotherapeutic treatments. Herein, we have developed novel Ru(II)/Ir(III)-mediated triazolylpyridine complexes as ROS inducers. Upon entering TNBC cells, Ru(II) complex effectively accumulated mitochondria triggered creation ROS, facilitating dysfunction oxidative DNA damage, ultimately causing cells through G2/M phase cycle arrest. Eventually, this induced upregulation BAX (pro-apoptotic protein) downregulation BCL-2 (antiapoptotic caspase 3/9 pathway released cytochrome c cytosol for apoptosis. JRu (RuII triazolylpyridine) significantly reduced integrity viability 3D spheroids.

Language: Английский

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Photodynamic Therapy Review: Past, Present, Future, Opportunities and Challenges

Photochem, Journal Year: 2024, Volume and Issue: 4(4), P. 434 - 461

Published: Oct. 1, 2024

Photodynamic therapy (PDT) is a medical treatment that utilizes photosensitizing agents, along with light, to produce reactive oxygen species can kill nearby cells. When the photosensitizer exposed specific wavelength of it becomes activated and generates destroy cancer cells, bacteria, other pathogenic micro-organisms. PDT commonly used in dermatology for treating actinic keratosis, basal cell carcinoma, skin conditions. It also being explored applications oncology, such as esophageal lung cancers, well ophthalmology age-related macular degeneration. In this study, we provide comprehensive review PDT, covering its fundamental principles mechanisms, critical components function. We examine key aspects including current clinical potential future developments. Additionally, discuss advantages disadvantages addressing various challenges associated implementation optimization. This aims offer thorough understanding highlighting transformative treatments while acknowledging areas requiring further research development.

Language: Английский

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Enhanced Anticancer Selectivity of Cyclometalated Imidazole/Pyrazole-Imine Iridium^III Complexes Through the Switch from Cationic to Zwitterionic Forms

Inorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

Cyclometalated iridiumIII complexes have shown promising anticancer properties, with variations in charge and ligand substitution significantly influencing their biological activity. However, zwitterionic remain scarcely explored. Herein, we report a series of cyclometalated imidazole/pyrazole-imine compare activity to analogous cationic sulfonate counteranions. X-ray crystallography confirmed the structural differences between forms. These exhibited cytotoxicity against A549, HeLa, HepG2 cancer cells, IC50 values ranging from 14.35 69.12 μM. While showed higher cytotoxicity, demonstrated enhanced selectivity for A549 cells over BEAS-2B normal (selectivity index: 3.72-5.90 forms vs 1.16-1.44 forms). This is attributed distinct cellular uptake mechanisms: use an energy-dependent pathway energy-independent leading accumulation redox Mechanistic studies revealed that both complex types induce ROS generation mitochondrial membrane depolarization (MMP), apoptosis as primary cell death pathway.

Language: Английский

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Instigating Visible Light Inspired DNA Impairment by ROS Harvesting Ir(III)‐Cyclometallated Imidazophenanthroline Complexes Against MDA‐MB‐231 Cells

European Journal of Inorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Abstract Difficulties to abate the vehemence of deleterious triple‐negative breast cancer (TNBC) is an ardent issue in current context anticancer research due lack a selective treatment modality. To address this issue, herein we have endeavored establish imidazophenanthroline‐based Ir(III)‐cyclometallated heteroleptic complexes, suited for one‐photon photodynamic therapy (OP‐PDT) under irradiation visible light (400–700 nm) possessing long‐lived excited triplet state and significant photostability. Among three synthesized [ L1Ir ], L2Ir L3Ir complex ] has been recognized as most competent exhibit phototoxicity (IC 50 =3.8 μ M; PI c =78.94) MDA‐MB‐231 cells. The complexes arisen production reactive singlet oxygen ( 1 O 2 ) following type‐II pathway (Φ s =0.26). Also, shown proficiency oxidation reduced nicotinamide adenine dinucleotide (NADH) (TOF=4.35 h −1 indicating possibility species (O ⋅ − , ⋅OH) generation through type‐I upon irradiation. Along with this, intracellular glutathione (GSH) depletion capabilities endued unarm TNBC cells front profuse amount ROS instigating programmed cell death (PCD) substantial DNA damage.

Language: Английский

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Intracellular Photocatalytic NADH/NAD(P)H Oxidation for Cancer Drug Development

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: 147(9), P. 7161 - 7181

Published: Feb. 20, 2025

Photocatalytic cancer therapy (PCT) has emerged as a cutting-edge anticancer mechanism of action, harnessing light energy to mediate the catalytic oxidation intracellular substrates. PCT is significant current importance due its potential address limitations conventional chemotherapy, particularly drug resistance and side effects. This approach offers noninvasive, targeted treatment option by utilizing metal-based photocatalysts induce redox metabolic disorders within cells. The disrupt cell metabolism converting NADH/NAD(P)H NAD+/NAD(P)+ via photoredox processes, altering NAD+/NADH or NAD(P)+/NAD(P)H ratios, which are crucial for cellular metabolism. Ir(III), Ru(II), Re(I), Os(II) demonstrated promising efficacy. Despite these developments, gaps remain in literature translating this new into clinical trials. Perspective critically examines developments research area provides future directions designing efficient PCT.

Language: Английский

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Anticancer potential of polypyridyl-based Ir(III)-coumarin 6 conjugates under visible light and dark

Inorganic Chemistry Communications, Journal Year: 2025, Volume and Issue: unknown, P. 114184 - 114184

Published: Feb. 1, 2025

Language: Английский

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Rationally Designed Ir(III) Complex with an Exceptionally Strong Binding to Human Serum Albumin for Targeted Photodynamic Therapy

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

The application of iridium(III) complexes in photodynamic therapy (PDT) is often limited by their poor selectivity for cancerous cells, necessitating high drug doses that increase the risk side effects. development efficient delivery systems such as albumin conjugation therefore crucial to enhance tumor-targeted photosensitizers. To date, vast majority metal exhibit weak moderate binding with human serum albumin, limiting feasibility this approach. overcome limitation, rational design through molecular docking and density functional theory calculations a novel Ir(III) complex strong albumin-binding photosensitizer described. herein reported compound has highest constant ever an iridium complex, it showed photocatalytically produce reactive oxygen species upon blue light irradiation. presented well structural derivatives could have potential therapy.

Language: Английский

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Tri-emissive red-green dye-encapsulated UiO-66-Ph as a white-light emission fluorescence sensor for Fe3+ and Cr2O72− detection in environmental water samples

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy, Journal Year: 2025, Volume and Issue: 339, P. 126301 - 126301

Published: April 26, 2025

Language: Английский

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Recent advances in Rh(III)-based anticancer complexes

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 525, P. 216306 - 216306

Published: Nov. 22, 2024

Language: Английский

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Vitamin B6 appended polypyridyl Co(III) complexes for photo‐triggered antibacterial activity

Chemistry - An Asian Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 11, 2024

Abstract Three novel polypyridyl‐Co(III)‐vitamin B 6 complexes viz ., [Co(CF 3 ‐phtpy)(SBVB )]Cl ( Co1 ), [Co(anthracene‐tpy)(SBVB Co2 [Co(NMe 2 Co3 where 4’‐(4‐(trifluoromethyl)phenyl)‐2,2’:6’,2’’‐terpyridine=CF ‐phtpy, 4’‐(anthracen‐9‐yl)‐2,2’:6’,2’’‐terpyridine=anthracene‐tpy;, 4‐([2,2’:6’,2’’‐terpyridin]‐4’‐yl)‐N,N‐dimethylaniline=NMe (E)‐5‐(hydroxymethyl)‐4‐(((2‐hydroxyphenyl)imino)methyl)‐2‐methylpyridin‐3‐ol=H SBVB were successfully developed for aPDT (antibacterial photodynamic therapy) applications. – exhibited an intense absorption band at ca . 435–485 nm, which is attributed to ligand‐to‐metal charge transfer and was beneficial antibacterial therapy. The distorted octahedral geometry of the with Co III N 4 O core evident from DFT study. visible light ability good photo‐stability made them photosensitizers aPDT. displayed significant responses against gram‐positive S. aureus ) gram‐negative E. coli bacteria upon exposure (10 J cm −2 , 400–700 nm) showed MIC values between 0.01–0.005 μg mL −1 activities these due their damage bacterial cell membranes via ROS generation. Overall, this study shows photo‐triggered ROS‐mediated bacteria‐killing potential Co(III) complexes.

Language: Английский

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