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Exploring Covalency in f-Element Complexes: Dithiocarbamate Ligands Reveal Differences Between Heavy Actinides and Lanthanides.

Covalence in f-elements plays a pivotal role in distinguishing the fundamental properties of actinides and lanthanides. In this study, trivalent and tetravalent actinide (U-Fm) and lanthanide (Nd-Er) complexes with dithiocarbamate (S2CNH2-) ligands were systematically analyzed. Various methodologies were employed, notably Slater-Condon parameters, metrics in bond critical points (BCP) under the quantum theory of atoms in molecules (QTAIM) framework, and natural localized molecular orbitals (NLMOs). The multiconfigurational nature of the systems and the scalar relativistic and spin-orbit coupli…

Coumarin Ligands Regulate Excited-State Intersystem Crossing Processes of Ir(III)-Based Transition Metal Complexes.

Iridium(III)-based transition metal complexes (TMCs) have attracted much attention due to their excellent photophysical properties (i.e., powerful visible light trapping ability, ultrafast intersystem crossing (ISC) processes, long-lived triplet excited states, etc.) and show promising applications in energy, materials, and biotechnology. The photophysical properties of Ir(III)-based TMCs are highly related to those of their ligands. Revealing the photophysical mechanisms of these Ir(III)-based TMCs is crucial for elucidating the excited-state behavior and regulating the properties of these TM…

Dictating nanorod assembly via the hydrophilic/hydrophobic transition of polymer ligands based on Hofmeister effect.

Self-organization of anisotropic nanostructures into polymer/inorganic superstructures are of great research interest for various applicatio … ypical kosmotropic ions, we can precisely modulate the hydrophilic-to-hydrophobic transition of PEG ligands by the dehydration of PEG polymer ligands, enabling controlled nucleation and growth of nanorods in solution. The weak hydrophobicity of PEG ligands drives lying-down nanorods to form 2D smectic liquid crystalline phases, which serves as templates f …

The Evolution of AChE Inhibitors in Alzheimer's Disease: From Single-Target to Multi-Target Ligands.

Alzheimer's disease (AD) is a chronic neurodegenerative disease marked by cognitive decline, neuronal degeneration, and the accumulation of intracellular neurofibrillary tangles, extracellular amyloid plaques, and neuroinflammation. Current treatment strategies, such as acetylcholinesterase inhibitors (AChEIs) and N-methyl-D-aspartate receptor antagonists, offer symptomatic relief but fail to stop disease progression. The development of multi-target-directed ligands (MTDLs) has gained attention as a method to address the complex pathology of AD. This review provides a detailed account of the j…

Data on the docking of millet-derived secondary metabolites as multi-target ligands for diabetes.

The deterioration of human health due to unhealthy lifestyle and dietary habits has led to a worldwide increase in various metabolic disease … t strategy. This approach utilises network pharmacology and screening methods to identify potential ligands that act as inhibitors for the treatment of complex, interconnected diseases. In the current investigation, we used a molecular docking approach to investigate secondary metabolites from millet as potential multi-target ligands for the treatment of …

Virtual High-Throughput Screening of Ligands for Disrupting PRMT5/pICLn Interaction in Prostate Cancer Cells.

Prostate cancer (PC) is the most commonly diagnosed cancer in men worldwide. While androgen deprivation therapy (ADT) is initially effective, many patients develop resistance, progressing to castration-resistant prostate cancer (CRPC). Recent studies have identified the interaction between PRMT5 (protein arginine methyltransferase 5) and pICLn as a promising therapeutic target, as it promotes the transcription of double-strand break (DSB) repair genes that contribute to therapy resistance. To target this pathway, a screening campaign identified J021-0199 as a potential hit compound that disrup

Integrated phenotypic screening and chemical proteomics identifies ETF1 ligands that modulate viral translation and replication.

UNLABELLED: Emerging and re-emerging viruses pose a significant threat to global health. Although direct-acting antivirals have shown succes … somal frameshifting mechanisms. Our findings thus identify a mechanistically distinct class of ETF1 ligands that implicate host translation termination processes as a potential target for antiviral development. SIGNIFICANCE STATEMENT: The identification of broad-spectrum antivirals that target host proteins is a desirable strategy to combat emerging vira …

Unsymmetrical bis(anilido)xanthene ligands: development and use in the preparation of magnesium diamide complexes.

Unsymmetrical bis(anilido)xanthene ligands, decorated by a 2,4,6-tricyclohexylanilido substituent and a less bulky anilido group, are readily prepared in moderate yields from a 4,5-dibromo-substituted xanthene. These ligands are used for the preparation of magnesium(II) complexes, the reductions of which in methylcyclohexane and benzene are described.

Versatile applications of cobalt and copper complexes of biopolymeric Schiff base ligands derived from chitosan.

In the present study, biopolymeric Schiff base (SB) ligands were synthesized from chitosan and isatin. Consequently, their earth abundant transition metal complexes of cobalt and copper were synthesized. All compounds were extensively characterized using FTIR and UV spectroscopy, thermo-gravimetric (TG) analysis, X-ray powder diffraction (XRD) and FESEM (field emission scanning electron microscopy). The impetus of this study was to explore different applications of the same transition metal complexes, thereby converting them to broad spectrum antimicrobial drugs and to useful chemical catalyst…

Self-assembly of azamacrocyclic ligands into vesicular structures: from design to functional properties and applications.

We report on the design and synthesis of novel scorpiand-like macrocyclic ligands that self-assemble into vesicular structures. These ligands, derived from a 6-(2-aminoethyl)-3,6,9-triaza-1-(2,6)-pyridinacyclo-decaphane scaffold, are functionalized with hydrophobic alkyl chains to facilitate vesicle formation. Their properties in solution and their complexation with Cu(II) are thoroughly investigated. These supramolecular assemblies were characterized using TEM and DLS. The studied systems were non-toxic as inferred from an HET-CAM assay. Additionally, the copper complexes exhibit varying degr…

Employing phosphonate and phosphinate ligands for prodrug development of the mitochondrial calcium uniporter inhibitor Ru265.

Ru265, [Ru2(μ-N)(NH3)8Cl2]Cl3, is a potent nanomolar inhibitor of the mitochondrial calcium uniporter (MCU), the transporter that mediates Ca2+ uptake into the mitochondria. This compound and related MCU inhibitors are promising therapeutic agents and chemical biology tools for studying intracellular Ca2+ dynamics. Axial ligand modification of these Ru-based complexes provides a facile way to tune their properties and make prodrugs. In this study, the use of axial phosphonate and phosphinate ligands was explored within this compound class, yielding [Ru2(μ-N)(NH3)8(OPO(OH)Me)2](CF3SO3)3 (1) and…

Calcium Channel α2δ Ligands Mirogabalin, Pregabalin, and Gabapentin: Advancements in Diabetic Peripheral Neuropathic Pain Therapeutics.

Diabetic peripheral neuropathic pain (DPNP) is becoming increasingly prevalent as the global burden of diabetes continues to rise. DPNP manifests moderate-to-severe pain with burning, shooting, and tingling sensations, which increase clinical and economic burden and reduce the quality of life (QoL). α2δ ligands were developed on the basis of their mechanism of action involving the modulation of voltage-gated calcium channels (VGCCs). These ligands bind to the α2δ subunit of VGCCs, which reduces calcium influx and subsequently decreases the release of excitatory neurotransmitters. A majority of…

Fragment-based discovery and optimization of Zika virus NS3 helicase ligands as antiviral hit candidates.

Mosquito-borne flaviviruses, such as Zika virus (ZIKV), pose significant public health challenges, with no approved vaccines or therapeutics available. The ZIKV non-structural protein 3 (NS3) helicase domain (NS3Hel) is a key target due to its critical role in viral RNA replication. In this study, we used high-throughput crystallographic fragment screening to identify ligands binding to NS3Hel. Four fragments, including hydantoin, oxadiazole, and phenylurea moieties, were selected for synthesis, structural modification, fragment growing and linking strategies. Biophysical and biochemical assay…

NKG2D receptor ligands are cell surface biomarkers for injured murine and human nociceptive sensory neurons.

Nociceptors are primary afferent neurons that sense noxious stimuli. They can be activated by tissue injury as well as the accompanying local immune response. We have shown that following nerve injury in mice, cytotoxic Natural Killer (NK) cells infiltrate the peripheral nerve where they interact with stress-induced ligands of the activating receptor NKG2D (Klrk1). However, the diversity and specificity of NKG2D receptor ligands among sensory neuron subtypes, and translation of this mechanism to human cells, remains unknown. We used dorsal root ganglion (DRG) neurons cultured from C57BL/6J mic…

Discovery of environment-sensitive fluorescent ligands for SHP2 imaging in living cells and tumor sections.

SHP2, a non-receptor protein tyrosine phosphatase, is a key regulator of the cellular signal transduction pathways. Its dysregulation has been associated with the pathogenesis of various diseases, notably cancers. In this study, we developed a series of small-molecule fluorescent probes targeting the allosteric site of SHP2 for the first time, which resulted in high affinity and specific SHP2 binding. These probes exhibited a significant Stokes shift, which was crucial for minimizing the phototoxicity and ensuring superior imaging quality. SHP-PS2, the top-performing probe, exhibited an IC50 o

Применяемые на основе хлороиндазола эстрогенные рецепторы β лиганды с благоприятными фармакокинетиками способствуют функциональному восстановлению и визуальному восстановлению.

Множественный склероз (MS) — хроническая аутоиммунная, демиелинационная и нейродегенеративная болезнь, приводящая к моторным, визуальным и когнитивным недостаткам. Хотя существующие методы лечения могут замедлить прогресс в области заболеваний, они редко восстанавливают утраченную неврологическую функцию или значительно повышают качество жизни. Эстроген рецептор β (ERβ) стал многообещающей терапевтической целью, поскольку он способен активировать неклассические каналы сигнала, связанные с нейрозащитой, иммунной модуляцией и ремиэлированием. В этом исследовании были выявлены два ERβ-селективных

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune, demyelinating, and neurodegenerative disease that results in motor, visual, and cognitive d … ection, immune modulation, and remyelination. In this study, two chloroindazole-based ERβ-selective ligands, K102 and K110, were identified for their favorable pharmacokinetic profiles and performance in preclinical absorption, distribution, metabolism, and elimination (ADME) screening. These compounds demonstrated biological activity by promoting oligode …

Engineering Core/Ligands Interfacial Anchors of Nanoparticles for Efficiently Inhibiting Both Aβ and Amylin Fibrillization.

Accurate construction of artificial nano-chaperones' structure is crucial for precise regulation of protein conformational transformation, facilitating effective treatment of proteopathy. However, how the ligand-anchors of nano-chaperones affect the spatial conformational changes in proteins remains unclear, limiting the development of efficient nano-chaperones. In this study, three types of gold nanoparticles (AuNPs) with different core/ligands interface anchor structures (Au─NH─R, Au─S─R, and Au─C≡C─R, R = benzoic acid) are synthesized as an ideal model to investigate the effect of interfaci…

Балансирование иммунотерапии рака клеток CIK и PPAR Ligands: One Потенциальное терапевтическое приложение для злоумышленников CNS.

Клеточная терапия, вызванная цитокином (CCK), оказалась успешной в клинических испытаниях на глиобластому. Не менее важное значение имеют и … еточной иммунотерапией с усиленным лизисом клеток CIK Мы представляем доказательства того, что PPAR ligands в сочетании с иммунотерапией CIK могут стать ценным вариантом для злокачественных опухолей CNS.

Benzylpiperidine derivatives as new dual μ-opioid and σ1 receptor ligands with potent antinociceptive effects.

Dual-acting μ-opioid receptor (MOR)/sigma-1 receptor (σ1R) ligands have displayed promise in exerting robust antinociceptive effects while reducing opioid-related side effects. To discover safer and more effective analgesics, we designed, prepared, and evaluated 30 benzylpiperidine derivatives as dual MOR and σ1R ligands. The obtained benzylpiperidine analogs were tested for MOR and σ1R binding affinity in vitro. The best compound 52 showed high affinity for both MOR [Ki (MOR) = 56.4 nM] and σ1R [Ki (σ1R) = 11.0 nM] and produced potent antinociceptive effects in the abdominal contraction test …

Gold(I) and Silver(I) Complexes Containing Hybrid Sulfonamide/Thiourea Ligands as Potential Leishmanicidal Agents.

Leishmaniasis is a group of parasitic diseases with the potential to infect more than 1 billion people; however, its treatment is still old and inadequate. In order to contribute to changing this view, this work consisted of the development of complexes derived from MI metal ions with thioureas, aiming to obtain potential leishmanicidal agents. The thiourea ligands (HLR) were obtained by reactions of p-toluenesulfohydrazide with R-isothiocyanates and were used in complexation reactions with AgI and AuI, leading to the formation of complexes of composition [M(HLR)2]X (M = Ag or Au; X = NO3- or …