Anticancer Activity of Metallodrugs and Metallizing Host Defense Peptides—Current Developments in Structure-Activity Relationship

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 7314 - 7314

Опубликована: Июль 3, 2024

This article provides an overview of the development, structure and activity various metal complexes with anti-cancer activity. Chemical researchers continue to work on development synthesis new molecules that could act as anti-tumor drugs achieve more favorable therapies. It is therefore important have information about chemotherapeutic substances their mode action. review focuses metallodrugs contain a key structural fragment, cisplatin paving way for application. The text also looks at ruthenium complexes, including therapeutic applications phosphorescent ruthenium(II) emphasizing dual role in therapy diagnostics. In addition, antitumor activities titanium gold derivatives, side effects, ongoing research improve efficacy reduce adverse effects are discussed. Metallization host defense peptides (HDPs) ions highlighted strategy significantly enhances anticancer by broadening mechanisms

Язык: Английский

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Reactive oxygen species and its role in pathogenesis and resistance to therapy in acute myeloid leukemia

Cancer Drug Resistance, Год журнала: 2024, Номер unknown

Опубликована: Фев. 22, 2024

Relapse following a short clinical response to therapy is the major challenge for management of acute myeloid leukemia (AML) patients. Leukemic stem cells (LSC), as source relapse, have been investigated their metabolic preferences and alterations at time relapse. As LSC rely on oxidative phosphorylation (OXPHOS) energy requirement, reactive oxygen species (ROS), by-products OXPHOS, role in effectiveness standard AML therapy. Increased levels non-mitochondrial ROS, generated by nicotinamide adenine dinucleotide phosphate oxidase, subgroup patients add complexity studying ROS. Although there are various studies presenting contribution ROS pathogenesis, resistance, its inhibition or activation target, model that can clearly explain has not conceptualized. This due heterogeneity AML, dynamics production, which influenced factors such type treatment, cell differentiation state, mitochondrial activity, also heterogeneous generation limited available data interaction with microenvironment. review summarizes these challenges recent progress this field.

Язык: Английский

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Phosphate-Buffered Saline and Dimethyl Sulfoxide Enhance the Antivenom Action of Ruthenium Chloride against Crotalus atrox Venom in Human Plasma—A Preliminary Report

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6426 - 6426

Опубликована: Июнь 11, 2024

Ruthenium chloride (RuCl3) is widely utilized for synthesis and catalysis of numerous compounds in academia industry as a key molecule variety with medical applications. Interestingly, RuCl3 has been demonstrated to modulate human plasmatic coagulation serves constituent compounded inorganic antivenom that neutralizes the coagulopathic effects snake venom vitro vivo. Using thrombelastography, this investigation sought determine if inhibition fibrinogenolytic Crotalus atrox could be modulated by vehicle composition plasma. Venom was exposed 0.9% NaCl, phosphate-buffered saline (PBS), or NaCl containing 1% dimethyl sulfoxide (DMSO). inhibited venom-mediated delay onset thrombus formation, decreased clot growth velocity, strength. PBS DMSO enhanced RuCl3. It concluded while Ru-based cation responsible significant activity, combination ions phosphate enhances RuCl3-mediated inhibition. Additional indicated what specific Ru-containing molecules cause other combinations inorganic/organic may enhance

Язык: Английский

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From Intercalation to External Binding: Ru(II) Complexes with a Spiro Ligand for TAR RNA Selective Binding and HIV-1 Reverse Transcriptase Inhibition

Inorganic Chemistry, Год журнала: 2024, Номер 63(26), С. 12342 - 12349

Опубликована: Июнь 21, 2024

As a typical RNA virus, the genetic information on HIV-1 is entirely stored in RNA. The reverse transcription activity of transcriptase (RT) plays crucial role replication and transmission virus. Non-nucleoside RT inhibitors (NNRTIs) block function by binding to site RT, with very few targeting viral In this study, transforming planar conjugated ligands into spiro structure, we convert classical Ru(II) DNA intercalators nonintercalator. This enables selective transactivation response (TAR) outer side nucleic acids through dual interactions involving hydrogen bonds electrostatic attraction, effectively inhibiting serving as fluorescence probe for TAR

Язык: Английский

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Ruthenium p-Cymene Complexes Incorporating Substituted Pyridine–Quinoline-Based Ligands: Synthesis, Characterization, and Cytotoxic Properties

Molecules, Год журнала: 2024, Номер 29(13), С. 3215 - 3215

Опубликована: Июль 6, 2024

Organometallic complexes of the formula [Ru(N^N)(p-cymene)Cl][X] (N^N = bidentate polypyridyl ligands, p-cymene 1-methyl-4-(1-methylethyl)-benzene, X counter anion), are currently studied as possible candidates for potential treatment cancer. Searching new organometallic compounds with good to moderate cytotoxic activities, a series mononuclear water-soluble ruthenium(II)–arene incorporating substituted pyridine–quinoline pending -CH2OH, -CO2H and -CO2Me groups in 4-position quinoline ring, were synthesized, first time, study their effect modulate activity ruthenium complexes. These include [Ru(η6-p-cymene)(pqhyme)Cl][X] (X Cl− (1-Cl), PF6− (1-PF6), pqhyme 4-hydroxymethyl-2-(pyridin-2-yl)quinoline), [Ru(η6-p-cymene)(pqca)Cl][Cl] ((2-Cl), pqca 4-carboxy-2-(pyridin-2-yl)quinoline), [Ru(η6-p-cymene)(pqcame)Cl][X] (3-Cl), (3-PF6), pqcame 4-carboxymethyl-2-(pyridin-2-yl)quinoline) complexes, respectively. Identification was based on multinuclear NMR ATR-IR spectroscopic methods, elemental analysis, conductivity measurements, UV–Vis spectroscopic, ESI-HRMS techniques. The solid-state structures 1-PF6 3-PF6 have been elucidated by single-crystal X-ray diffraction revealing three-legged piano stool geometry. This is time that vitro activities these studied. conducted HEK293T (human embryonic kidney cells) HeLa cells (cervical cancer via MTT assay. results show poor anticancer cell lines 3-Cl proved be most potent (IC50 > 80 μΜ). In both lines, cytotoxicity ligand precursor significantly higher than cisplatin.

Язык: Английский

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Phаrmacological Activity of Metal-Based Organic Complexes Against Different Viral Diseases

Pharmacophore, Год журнала: 2024, Номер 15(3), С. 1 - 11

Опубликована: Янв. 1, 2024

Язык: Английский

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N‐Heterocyclic Carbene Complexes Ru^II(Arene) and their Application as ROMP Catalysts, Antioxidant and Anticancer Agents

European Journal of Inorganic Chemistry, Год журнала: 2024, Номер 27(34)

Опубликована: Авг. 16, 2024

Abstract N‐Heterocyclic carbenes (NHCs) play an important role in metal complex catalysis and stabilisation, providing stability under non‐inert conditions a high σ‐donor capacity. They are crucial ligands for the synthesis of organometallic compounds like Ru II ‐complexes, which can operate as very active catalysts variety chemical transformations functionalizations. RA(Ruthenium‐arene)NHC complexes, known their piano‐stool structure, stabilise Ru(II) oxidation state by occupying three ruthenium coordination sites with η 6 ‐coordinated arene ligand. The development dual‐acting ‐arene complexes has sparked increased interest catalytic biological properties. Because broad spectrum, give distinct mechanisms pharmacological action from organic drugs. This study aimed to explore impact ligand amphiphilicity counterion on bioactivity, designing family NHC bearing ester moiety switching wingtip substituent methyl benzyl units. All synthesized were tested norbornene ROMP, benchmark reaction potential anticancer antioxidant compounds.

Язык: Английский

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Metal ions in biomedically relevant macromolecular structures

Frontiers in Chemistry, Год журнала: 2024, Номер 12

Опубликована: Авг. 23, 2024

Understanding the functions of metal ions in biological systems is crucial for many aspects research, including deciphering their roles diseases and potential therapeutic use. Structural information about molecular or atomic details these interactions, generated by methods like X-ray crystallography, cryo-electron microscopy, nucleic magnetic resonance, frequently provides that no other method can. As with any experimental method, they have inherent limitations sometimes lead to an erroneous interpretation. This manuscript highlights different structural data available metal-protein complexes. We examine quality modeling ion binding sites across structure determination methods, where kinds errors stem from, how can impact correct interpretations conclusions.

Язык: Английский

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Novel heteroleptic ruthenium complexes incorporating 6,7-dichloro-2,3-di(pyridine-2-yl)quinoxaline as polypyridyl bridging ligand: Synthesis, characterization, photophysical, electrochemistry, in vitro biological activity and molecular docking studies

Journal of Molecular Structure, Год журнала: 2024, Номер 1323, С. 140748 - 140748

Опубликована: Ноя. 16, 2024

Язык: Английский

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Microtubule-Targeting NAP Peptide-Ru(II)-polypyridyl Conjugate As a Bimodal Therapeutic Agent for Triple Negative Breast Carcinoma

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Дек. 26, 2024

Triple-negative breast cancer (TNBC) poses significant treatment challenges due to its high metastasis, heterogeneity, and poor biomarker expression. The N-terminus of an octapeptide NAPVSIPQ (NAP) was covalently coupled a carboxylic acid derivative Ru(2,2′-bipy)32+ (Rubpy) synthesize N-stapled short peptide-Rubpy conjugate (Ru-NAP). This photosensitizer (PS) utilized treat TNBC through microtubule (MT) targeted chemotherapy photodynamic therapy (PDT). Ru-NAP formed more elaborate molecular aggregates with fibrillar morphology as compared NAP. A much higher binding affinity over NAP toward β-tubulin (KRu-NAP: (6.8 ± 0.55) × 106 M–1; KNAP: (8.2 1.1) 104 M–1) observed stronger electrostatic interactions between the MT average linear charge density ∼85 e/nm cationic Rubpy part Ru-NAP. also supported by docking, simulation, appropriate imaging studies. promoted serum stability, specific E-site βIII-tubulin followed disruption network, effective singlet oxygen generation in cells (MDA-MB-231), causing cell cycle arrest G2/M phase triggering apoptosis. Remarkably, MDA-MB-231 were sensitive noncancerous human embryonic kidney (HEK293 cells) when exposed light (LightIC50Ru-NAP[HEK293]: 17.2 2.5 μM, LightIC50Ru-NAP[MDA-MB-231]: 32.5 7.8 nM, DarkIC50Ru-NAP[HEK293]: > 80 DarkIC50Ru-NAP[MDA-MB-231]: 2.9 0.5 μM). effectively inhibited tumor growth xenograft models nude mice. Our findings provide strong evidence that has potential therapeutic role treatment.

Язык: Английский

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