Metal N-heterocyclic carbene complexes as potential metallodrugs in antitumor therapy

Coordination Chemistry Reviews, Год журнала: 2024, Номер 514, С. 215941 - 215941

Опубликована: Май 18, 2024

Язык: Английский

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A promising future of metal‐N‐heterocyclic carbene complexes in medicinal chemistry: The emerging bioorganometallic antitumor agents

Medicinal Research Reviews, Год журнала: 2024, Номер 44(5), С. 2194 - 2235

Опубликована: Апрель 9, 2024

Abstract Metal complexes based on N ‐heterocyclic carbene (NHC) ligands have emerged as promising broad‐spectrum antitumor agents in bioorganometallic medicinal chemistry. In recent decades, studies cytotoxic metal–NHC yielded numerous compounds exhibiting superior cytotoxicity compared to cisplatin. Although the molecular mechanisms of these anticancer are not fully understood, some potential targets and modes action been identified. However, a comprehensive review their biological is currently absent. general, apoptosis caused by metal–NHCs common tumor cells. They can cause series changes after entering cells, such mitochondrial membrane (MMP) variation, reactive oxygen species (ROS) generation, cytochrome c (cyt c) release, endoplasmic reticulum (ER) stress, lysosome damage, caspase activation, ultimately leading apoptosis. Therefore, detailed understanding influence cancer cell crucial. this review, we provide summary advances that trigger apoptotic death via different apoptosis‐related or signaling pathways, including B‐cell lymphoma 2 (Bcl‐2 family), p53, cyt c, ER thioredoxin reductase (TrxR) inhibition, so forth. We also discuss challenges, limitations, future directions elucidate emerging application

Язык: Английский

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NHCs silver complexes as potential antimicrobial agents

Inorganica Chimica Acta, Год журнала: 2023, Номер 563, С. 121899 - 121899

Опубликована: Дек. 27, 2023

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Silver Organometallics that are Highly Potent Thioredoxin and Glutathione Reductase Inhibitors: Exploring the Correlations of Solution Chemistry with the Strong Antibacterial Effects

ACS Infectious Diseases, Год журнала: 2024, Номер 10(5), С. 1753 - 1766

Опубликована: Апрель 12, 2024

The antibacterial activity of silver species is well-established; however, their mechanism action has not been adequately explored. Furthermore, issues low-molecular compounds with cytotoxicity, stability, and solubility hamper progress to drug leads. We have investigated N-heterocyclic carbene (NHC) halido complexes [(NHC)AgX, X = Cl, Br, I] as a promising new type organometallics. Spectroscopic studies conductometry established higher stability for the iodide ligands, nephelometry indicated that could be administered in solutions physiological chloride levels. showed broad spectrum strong against pathogenic Gram-negative bacteria. However, there was no significant Gram-positive strains. Further clarified tryptone yeast extract, components culture media, were responsible this lack activity. reduction biofilm formation inhibition both glutathione thioredoxin reductases IC50 values nanomolar range confirmed selected compounds. In addition improved physicochemical properties, ligands did display cytotoxic effects, unlike other complexes. summary, NHC secondary represent useful scaffold nontoxic organometallics properties distinct based on reductases.

Язык: Английский

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N‐Heterocyclic Carbene (NHC) Silver Complexes as Versatile Chemotherapeutic Agents Targeting Human Topoisomerases and Actin

ChemMedChem, Год журнала: 2022, Номер 17(18)

Опубликована: Июль 29, 2022

In recent years, the number of people suffering from cancer has risen rapidly and World Health Organization U.S. European governments have identified this pathology as a priority issue. It is known that most bioactive anticancer molecules do not target single protein but exert pleiotropic effects, simultaneously affecting multiple pathways. our study, we designed synthesized new series silver N-heterocyclic carbene (NHC) complexes [(NHC)

Язык: Английский

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Biological Activities of Ruthenium NHC Complexes: An Update

Antibiotics, Год журнала: 2023, Номер 12(2), С. 365 - 365

Опубликована: Фев. 9, 2023

Ruthenium N-heterocyclic carbene (NHC) complexes have unique physico-chemical properties as catalysts and a huge potential in medicinal chemistry pharmacology, exhibiting variety of notable biological activities. In this review, the most recent studies on ruthenium NHC are summarized, focusing specifically antimicrobial antiproliferative generally active against Gram-positive bacteria, such Bacillus subtilis, Staphylococcus aureus, Micrococcus luteus, Listeria monocytogenes seldom Gram-negative including Salmonella typhimurium, Pseudomonas aeruginosa Escherichia coli fungal strains Candida albicans. The activity was tested cancer cell lines human colon, breast, cervix, epidermis, liver rat glioblastoma lines. demonstrated cytotoxicity higher than standard anticancer drugs. Further needed to explore mechanism action these interesting compounds.

Язык: Английский

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Bottom-Up Strategy to Forecast the Drug Location and Release Kinetics in Antitumoral Electrospun Drug Delivery Systems

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(2), С. 1507 - 1507

Опубликована: Янв. 12, 2023

Electrospun systems are becoming promising devices usable for topical treatments. They eligible to deliver different therapies, from anti-inflammatory antitumoral. In the current research, polycaprolactone electrospun membranes loaded with synthetic and commercial antitumoral active substances were produced, underlining how matrix-filler affinity is a crucial parameter designing drug delivery devices. Nanofibrous percentages of Dacarbazine (the choice melanoma) derivative produced compared AuM1, highly Au-complex low matrix. AFM morphologies showed that surface profile nanofibers affine similar one unloaded systems, thanks nature interaction. FTIR analyses proved efficacy interaction between amidic group polycaprolactone. AuM1-loaded membranes, because weak interaction, complex mainly aggregated in nanometric domains on nanofiber surface, which manifests roughness. Consequently, release profiles follow Fickian behavior Dacarbazine-based whereas two-step prominent burst effect was observed AuM1 systems. The performed tests evidence high-cytotoxic activity against melanoma cell lines, proving more than dacarbazine.

Язык: Английский

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In Silico SwissADME Analysis of Antibacterial NHC–Silver Acetates and Halides Complexes

Applied Sciences, Год журнала: 2024, Номер 14(19), С. 8865 - 8865

Опубликована: Окт. 2, 2024

This study investigates the antibacterial N-heterocyclic carbene (NHC)–silver complexes using SwissADME platform, a web-based tool developed by Swiss Institute of Bioinformatics (SIB). NHCs, particularly their silver complexes, have gained significant interest in medicinal chemistry for potential as and anticancer agents. The effectiveness these is closely linked to structure, including factors like lipophilicity, which enhance ability penetrate bacterial cells sustain release active ions. provides computational estimates pharmacokinetic properties, absorption, distribution, metabolism, excretion (ADME) characteristics, well drug-likeness toxicity assessments. By evaluating parameters molecular weight, topological polar surface area, lipophilicity (LogP), water solubility, offers insights into drug-like compounds. inspired comprehensive review NHC–silver published from 2006 2023, identified superior structures with notable biological activity. primary aim determine whether exhibit distinct compared others, providing deeper understanding that influence efficacy aiding identification promising drug candidates. Finally, experimental stabilities exemplary were confronted absolute LUMO values derived DFT calculations.

Язык: Английский

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Design, synthesis and biological evaluation of multitarget hybrid molecules containing NHC-Au(I) complexes and carbazole moieties

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 277, С. 116757 - 116757

Опубликована: Авг. 9, 2024

Язык: Английский

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Synergistic Antiproliferative Activity of Newly Synthesized Benzimidazole-Based Silver(I) Complexes on MCF-7 and T47D Cell Lines, CT-DNA Interactions Supported by Computational Studies

ACS Omega, Год журнала: 2025, Номер unknown

Опубликована: Март 28, 2025

This article reports the synthesis, characterization, and antitumor properties of newly synthesized benzimidazole-based Ag(I)-(BNHCs) complexes from their proligands. All compounds underwent comprehensive characterization using techniques such as 1H, COSY, 13C NMR, IR spectroscopy, electrospray ionization (ESI)-mass, elemental, single-crystal X-ray diffraction (XRD) analysis. Density functional theory (DFT) studies were carried out to observe electronic effects bound ligands modulate selectivity reactivity silver complexes. Time-dependent DFT (TD-DFT) assessed optical further highlighted by orbital contributions with oscillator strengths. tested against breast cancer MCF-7 T47D cell lines. The synergistic benzimidazole-incorporated aryl constituent structuring also observed. Nearly all have been found be promising anticancer agents added benefit low cytotoxic toward normal cells. Intriguingly, [AgL 4 (Cl)] exhibited best activity among our screened IC50 values for both 9 ± 1.04 11 1.41, respectively. apoptosis mode death was confirmed phosphatidylserine exposure annexin V/PI staining imaging method. CT-DNA interactions most active complex ([AgL (Cl)]) its proligand (HL (Cl)) support compound-DNA interaction. Strong DNA binding affinities (K b) through electrostatic intercalation modes induced structural changes in DNA. Moreover, molecular docking comprehend possible various receptors EGFR (epidermal growth factor receptor), VEGFR2 (vascular endothelial receptors), FGFR (fibroblast SRC (proto-oncogene tyrosine kinase protein) family serves crucial cancer.

Язык: Английский

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