ACS Publications最新文献

{"title":"Discovery of a Novel Orally Active Ketamine Derivative with Dual Analgesic and Antidepressant Activities, Lacking Psychomimetic Effects.","authors":"Syed Muzzammil Masaud, Humaira Nadeem, Babar Murtaza, Abida Shamim","doi":"10.1021/acschemneuro.4c00887","DOIUrl":"10.1021/acschemneuro.4c00887","url":null,"abstract":"<p><p>This study investigated the synthesis, characterization, and in silico analysis of novel <i>N</i>-acetamide ketamine derivatives aimed at evaluating their analgesic, anesthetic, and antidepressant properties. The synthesis commenced with the preparation of chloroacetylamide derivatives, which were subsequently reacted with ketamine hydrochloride, yielding 16 derivatives <b>k</b>_<b>1</b> to <b>k</b>_<b>16</b>. These compounds were characterized through H¹ NMR, C¹³ NMR, mass spectroscopy (EIMS), and elemental analysis, followed by an assessment of their physicochemical properties. The analgesic efficacy of all of the synthesized derivatives was evaluated using the acetic acid-induced writhing test via intraperitoneal administration. The best-performing molecule was further evaluated for analgesic (acetic acid-induced writhing test, tail suspension test (TST), and hot plate test) and anti-inflammatory (carrageenan-induced paw edema) activities. For antidepressant effects, all derivatives were compared with ketamine in a lipopolysaccharide-induced model of depression in mice through the forced swimming test, open field test (OFT), sucrose preference test (SPT), and TST. It was observed that among all the derivatives, molecule <b>k</b>_<b>1</b> demonstrated comparable analgesic activity to ketamine. Further, compound <b>k</b>_<b>1</b> also exhibited the highest antidepressant potential during the forced swimming test, OFT, SPT, and TST. <b>k</b>_<b>1</b> was further compared with ketamine for their activities intraperitoneally and orally where <b>k</b>_<b>1</b> exhibited comparable antidepressant effects to ketamine. Henceforth, the psychomimetic potential of <b>k</b>_<b>1</b> was evaluated through loss of righting reflex and Y-maze tests. Very interestingly, these tests indicated approximately no psychomimetic activity of <b>k</b>_<b>1</b> compared to ketamine intraperitoneally and orally. Finally, molecular docking studies were conducted targeting the NMDA receptor at the JC09 ketamine binding pocket (PDB ID: 7EU7), where all synthesized derivatives exhibited significant binding affinities relative to ketamine. These findings suggest that the newly synthesized <i>N</i>-acetamide ketamine derivative <b>k</b>_<b>1</b> possesses promising pharmacological profiles, warranting further exploration.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":"932-944"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sulfamerazine as a Potential Modulator against α-Synuclein Aggregation and Associated Toxicity.","authors":"Priyanka Singh, Nagesh Y Kadam, Rajlaxmi Panigrahi, Arpit Mehrotra, Krishna Upadhayay, Madhumita Dey, Arpit Tyagi, Muhammad Aquib, Janni Nielsen, Giulia Kleijwegt, Prashant Singh, Abhishek Sharma, Alka Rao, Daniel E Otzen, Ashutosh Kumar, Deepak Sharma","doi":"10.1021/acschemneuro.4c00803","DOIUrl":"10.1021/acschemneuro.4c00803","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. The presence of Lewy bodies, primarily consisting of amyloid aggregates of the protein α-synuclein (α-Syn), is a common feature seen in dopaminergic neurons in (PD) patients. In the present study, we screened 2320 FDA-approved drugs and found 3 lead molecules, sulfamerazine, lathosterol, and tamoxifen, that reproducibly inhibited α-Syn fibrillation. Dose-response studies showed that sulfamerazine and lathosterol are relatively more potent than tamoxifen in inhibiting α-Syn aggregation. Among the lead compounds, sulfamerazine showed a significant reduction in α-Syn aggregation and associated toxicity in <i>Caenorhabditis elegans</i> model of PD. Sulfamerazine also reduced the accumulation of α-Syn aggregates in neuronal SH-SY5Y cells. Microscale thermophoresis confirmed the binding of sulfamerazine to α-Syn. NMR studies corroborated the binding of sulfamerazine with α-Syn and show that upon interaction, α-Syn is sequestered into large soluble dispersed assemblies, which is similar to as seen in transmission electron microscopy. We conclude that sulfamerazine and its derivatives hold promise as therapeutic agents against Parkinson's disease.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":"880-894"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Perspective on Scientific Integrity: A Reflection on Methods, Mindsets, and Legacy.","authors":"Eugenio H Otal","doi":"10.1021/acs.jafc.5c01403","DOIUrl":"10.1021/acs.jafc.5c01403","url":null,"abstract":"","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":" ","pages":"4980-4981"},"PeriodicalIF":5.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Purinergic Receptor P2Y1 Modulates Catecholamine Signaling in Murine Mesenteric Lymph Nodes.","authors":"Alexandra K Brooke, Sarbeshwar Ojha, Daniel P Murrow, Ashley E Ross","doi":"10.1021/acschemneuro.4c00435","DOIUrl":"10.1021/acschemneuro.4c00435","url":null,"abstract":"<p><p>Neuroimmune communication is crucial for the body's response to physiological challenges, homeostasis, and immune stress response. Adrenergic and purinergic neurotransmission in the sympathetic nervous system is vital for this communication. This study achieves the first co-detection of adenine-based purines and catecholamines in mesenteric lymph nodes via fast-scan cyclic voltammetry. Additionally, we reveal that manipulating an ATP receptor can impact catecholamine signaling in the lymph node for the first time. The G-protein-coupled receptor P2Y1, which controls intracellular Ca²⁺ levels, was targeted with the antagonist MRS2179. MRS2179 decreased catecholamine concentrations, increased inter-event times, and prolonged event durations. These results suggest that events became smaller, less frequent, and longer-lasting, possibly attributable to decreased intracellular Ca²⁺ levels. These findings indicate that ATP release in the lymph node can partially regulate norepinephrine signaling, providing mechanistic insight into sympathetic neuronal neurotransmitter control. A deeper understanding of more complicated neuroimmune mechanisms could potentially influence the development of therapeutic strategies in immunology and neurobiology.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":"772-780"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Magic Size to Atomic Precision: Facile Synthesis of a CdTe Semiconductor Nanocluster.","authors":"Saryvoudh A Mech, Joshua O Gibson, Fuyan Ma, Lukasz M Dobrzycki, Chenjie Zeng","doi":"10.1021/jacs.4c16188","DOIUrl":"10.1021/jacs.4c16188","url":null,"abstract":"<p><p>Facile synthesis of atomically precise semiconductor nanoclusters remains an important challenge, especially for those with heavier chalcogens. Combining coordination and colloidal methods, we developed a simple approach for synthesizing an atomically precise CdTe nanocluster with high purity and stability. Specifically, a precise cadmium-thiolate compound, [Cd₄(SR)₉]_n, was reacted with a facile phosphine telluride (TePR₃) precursor to produce a CdTe magic-sized cluster with a distinct absorption peak at 377 nm and a narrow linewidth of 20 nm. X-ray crystallography reveals the cluster is Cd₃₂Te₁₄(SR)₃₆(PR₃)₄, a homologue of Cd₃₂S₁₄ and Cd₃₂Se₁₄ reported about three decades ago, thus filling the missing link in this family. The cluster features a zincblende core in a truncated tetrahedron shape. While the core is achiral, chirality emerges from the rotational stacking of surface ligands. The left and right enantiomers self-assemble into a highly ordered, atomically coherent cubic superlattice, leading to a rare racemic crystal coined as \"kryptoracemate.\" This method provides an accessible platform for further atomic engineering of CdTe and related nanoclusters toward their target applications.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":" ","pages":"7507-7512"},"PeriodicalIF":14.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temperature-Dependent Mixed Valency in the Hexagonal Perovskite Cs₃NaFe₂Cl₉.","authors":"David Liu, Alexander Milder, Jeremiah Stevens, Cierra Foster, Brendan Beck, Maxim Avdeev, Patrick M Woodward","doi":"10.1021/jacs.4c17019","DOIUrl":"10.1021/jacs.4c17019","url":null,"abstract":"<p><p>The hexagonal perovskites Cs₃NaFe₂Cl₉ and Cs₃NaMnFeCl₉ have been synthesized and investigated. Both compounds adopt the 6H perovskite structure with <i>P</i>6₃/<i>mmc</i> symmetry. This structure consists of dimers of face-sharing octahedra arranged on the vertices of a triangular network. The transition metal ions occupy sites in these octahedra, leading to Fe₂Cl₉^4- and FeMnCl₉^4- bioctahedra, respectively. The bioctahedral clusters are sandwiched by layers of corner-sharing octahedra occupied by Na⁺ cations. Diffuse reflectance spectroscopy reveals optical transitions that arise from metal-to-metal charge transfer (Cs₃NaMnFeCl₉) and intervalence charge transfer (Cs₃NaFe₂Cl₉) excitations. In Cs₃NaFe₂Cl₉, magnetic susceptibility measurements reveal local ferromagnetic coupling (θ_CW = 16.7 K), mediated by the rapid exchange of an electron between the iron sites within each dimer. In contrast, the magnetic coupling between Fe³⁺ and Mn²⁺ in Cs₃NaMnFeCl₉ is antiferromagnetic (θ_CW = -41.4 K). At 100 K, the Mössbauer spectrum is dominated by a single type of iron that corresponds to Fe^2.5+, signaling electron exchange between iron sites that is faster than the Mössbauer time scale (∼100 ns). Upon further cooling, the Fe^2.5+ signal gives way to a 1:1 ratio of Fe²⁺ and Fe³⁺, as the thermally activated hopping slows down.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":" ","pages":"7634-7643"},"PeriodicalIF":14.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterostructure Nanoscintillator for Matching Radiation Absorbing Layers with Fast Light-Emitting Layers.","authors":"Orr Be'er, Avner Shultzman, Rotem Strassberg, Georgy Dosovitskiy, Noam Veber, Roman Schuetz, Charles Roques-Carmes, Ido Kaminer, Yehonadav Bekenstein","doi":"10.1021/acs.nanolett.4c05353","DOIUrl":"10.1021/acs.nanolett.4c05353","url":null,"abstract":"<p><p>Fast-emitting scintillators are essential for advanced diagnostic techniques, yet many suffer from low radiation attenuation. This trade-off is particularly pronounced in polymer scintillators, which, despite their fast emission, exhibit low density and low atomic numbers, limiting the radiation attenuation factor, resulting in low detection efficiency. Here, we overcome this limitation by creating a heterostructure scintillator of alternating nanometric layers, combining fast light-emitting polymer scintillator layers and transparent stopping layers with a high radiation attenuation factor. The nanolayer thicknesses are tuned to optimize the penetration depth of recoil electrons in active emissive layers, maximizing the conversion of X-rays to visible light. This design increases light output by up to 1.5 times and enhances imaging resolution by a factor of 2 compared to homogeneous polymer scintillators due to the ability to use thinner samples. These results demonstrate the potential of heterostructure scintillators as next-generation detector materials, overcoming the limitations of homogeneous scintillators.</p>","PeriodicalId":53,"journal":{"name":"Nano Letters","volume":" ","pages":"3422-3429"},"PeriodicalIF":9.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metastable Phase Noble-Metal-Free Core-Shell Structure for Efficient Electrocatalytic Nitrobenzene Transfer Hydrogenation.","authors":"Yutian Xiong, Jinxin Chen, Yue Wang, Qun Wang, Da Liu, Qi Shao, Jianmei Lu","doi":"10.1021/acs.nanolett.4c04966","DOIUrl":"10.1021/acs.nanolett.4c04966","url":null,"abstract":"<p><p>In order to study the catalytic behavior of a metastable-phase catalyst in electrocatalytic hydrogenation, we report a new metastable-phase noble-metal-free core-shell catalyst with a metastable hexagonal closest packed (hcp) phase Ni as the shell and face-centered-cubic (fcc) phase Cu as the core (Cu@hcp Ni NPs) for electrocatalytic hydrogenation of nitrobenzene (Ph-NO₂) to aniline (Ph-NH₂). Using H₂O as the hydrogen source, it achieves up to 99.63% Ph-NO₂ conversion and ∼100% Ph-NH₂ selectivity, with an improved activity turnover frequency (TOF: 6640 h^-1), much higher than those of hcp Ni NPs (5183.7 h^-1) and commercial Pt/C (3537.6 h^-1). It can also deliver a variety of aminoarenes with outstanding selectivity and excellent functional group compatibility with several groups. Mechanistic studies have shown that the introduction of Cu enhances hcp Ni's ability to dissociate water <i>in situ</i> to produce H* and improves the hydrogenation rate, resulting in the rapid conversion of Ph-NO₂ to the final product Ph-NH₂.</p>","PeriodicalId":53,"journal":{"name":"Nano Letters","volume":" ","pages":"3383-3390"},"PeriodicalIF":9.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Luteolin Mitigates Acute Lung Injury Through Immune Modulation and Antinecroptosis Effects by Targeting the BTK and FLT3 Signaling Pathways.","authors":"Zhixing Cao, Huanan Rao, Wenya Yang, Xiaoxue Hu, Xin Kang, Daoyin Gong, Xiaominting Song, Yali Ren, Cheng Peng, Yuzhi Li, Jin Pei","doi":"10.1021/acs.jafc.4c06704","DOIUrl":"10.1021/acs.jafc.4c06704","url":null,"abstract":"<p><p>Overactive immune responses and lung cell damage exacerbate acute lung injury (ALI). Luteolin, a flavonoid commonly found in traditional herbs, shows potential as an anti-ALI agent in pharmacological and clinical research, although its biological mechanism is not fully understood. This study aims to investigate whether luteolin can ameliorate ALI through its immune-modulatory and antinecroptosis mechanisms. We found that luteolin significantly inhibits the cellular activity of the FLT3-dependent monocyte cell line MOLM-13 and BTK-dependent B-cell line TMD-8. Through molecular docking and HTRF detection, it was confirmed that luteolin inhibits BTK and FLT3 enzyme activity by binding to their kinase domains, with IC₅₀ values of 0.78 and 0.35 μM, respectively. In a TNF-α-induced lung epithelial cell injury model, luteolin reduced the increased expression of <i>IL1B</i>, <i>IL6</i>, and <i>CXCL8</i> mRNAs by blocking the necroptosis signal TNF-α/BTK/MLKL. Furthermore, using a Balb/c mouse ALI model with intratracheal LPS infusion (5 mg/kg), it was observed that luteolin improved lung function and pathology, regulated immune cell infiltration, and reduced cell death in pulmonary tissues by inhibiting BTK and FLT3 protein phosphorylation. In conclusion, luteolin acts as a natural BTK and FLT3 inhibitor, effectively preventing ALI both <i>in vivo</i> and <i>in vitro</i> through its immune-modulating and antinecroptosis properties.</p>","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":" ","pages":"5180-5193"},"PeriodicalIF":5.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PxSpätzle3 Regulates the Toll Pathway To Affect <i>Bacillus thuringiensis</i> Susceptibility of <i>Plutella xylostella</i>.","authors":"Yan Sun, Ji Yuan, Shuncai Han, Qiuping Wang, Muhammad Rehan Akhtar, Xiaofeng Xia","doi":"10.1021/acs.jafc.4c11380","DOIUrl":"10.1021/acs.jafc.4c11380","url":null,"abstract":"<p><p>Spätzle is an important messenger in the Toll pathway of the insect innate immune system. However, the function of Spätzle in regulating the Toll pathway in <i>Bacillus thuringiensis</i> (Bt) susceptibility of <i>Plutella xylostella</i> is unclear. In this study, we cloned the <i>Spätzle3</i> gene of <i>P. xylostella</i>. Molecular docking and yeast two-hybrid experiments indicated that PxSpätzle3 combined with PxToll6 to regulate the Toll pathway. After knocking out <i>PxSpätzle3</i>, the expression of downstream Toll pathway genes and antimicrobial peptides (AMPs) decreased. Antibacterial assays showed that PxGloverin2 could inhibit Bt8010. Further bioassays revealed that the susceptibility of the mutant to Bt8010 was significantly higher than that of the wild type. Intriguingly, the gut bacteria <i>Enterobacter</i> sp. EbPXG5 enhanced the lethality of Bt8010 to the mutant <i>P. xylostella</i>. Our findings clarify that PxSpätzle3 activates the Toll pathway by binding with PxToll6, regulates AMP production, and affects the susceptibility of <i>P. xylostella</i> to Bt8010. Additionally, our study uncovers the role of gut bacteria in this process. These insights provide new ideas for the sustainable control of pests.</p>","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":" ","pages":"5129-5139"},"PeriodicalIF":5.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}