ChemistryOpen最新文献_第4页

Synthesis of Sulfonamides in the Biobased Solvent Cyrene 生物基溶剂苯乙烯中磺胺类化合物的合成。

IF 3 4区化学

ChemistryOpen Pub Date : 2026-08-27 DOI: 10.1002/open.70290

Michela Galli, Andrea Fulminante, Alessandro Fiori, Valerio Fasano, Alessandra Silvani, Daniele Passarella, Andrea Citarella

{"title":"Synthesis of Sulfonamides in the Biobased Solvent Cyrene","authors":"Michela Galli, Andrea Fulminante, Alessandro Fiori, Valerio Fasano, Alessandra Silvani, Daniele Passarella, Andrea Citarella","doi":"10.1002/open.70290","DOIUrl":"10.1002/open.70290","url":null,"abstract":"A versatile protocol for the synthesis of sulfonamides using the biobased solvent Cyrene as reaction medium is reported. A wide range of primary and secondary amines were successfully employed, demonstrating the broad applicability of the method. The reactions proceed at room temperature and typically reach completion within 30–60 min. The resulting 20 sulfonamide products were isolated in good to high yields (up to 90%) by simple precipitation, upon addition of cold water and mild acid, without the need for chromatographic separation. The identified procedure offers an improved environmental profile, while maintaining high efficiency. Cyrene can be recovered and reused without loss of efficiency: Through a two-step extraction and filtration process, up to 79% of the solvent was successfully recovered and reused in a subsequent reaction cycle, furnishing the product in a yield comparable to that of the first cycle. Overall, this methodology provides a practical, mild, scalable, and more sustainable approach to sulfonamide synthesis.","PeriodicalId":9831,"journal":{"name":"ChemistryOpen","volume":"15 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/open.70290","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148825368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of Chalcone-Sulfonamide Hybrids as Antibacterial, Antioxidant, and Anti-Inflammatory Agents With Comprehensive In Silico and ADMET Profiling 作为抗菌、抗氧化和抗炎剂的查尔酮-磺酰胺杂化合物的合成及其综合硅和ADMET谱分析。

IF 3 4区化学

ChemistryOpen Pub Date : 2026-08-27 DOI: 10.1002/open.70292

Mlis Belete, Endale Mulugeta, Daniel Rentsch, Muhdin Aliye, Kebede Shenkutie, Yadessa Melaku

{"title":"Synthesis of Chalcone-Sulfonamide Hybrids as Antibacterial, Antioxidant, and Anti-Inflammatory Agents With Comprehensive In Silico and ADMET Profiling","authors":"Mlis Belete, Endale Mulugeta, Daniel Rentsch, Muhdin Aliye, Kebede Shenkutie, Yadessa Melaku","doi":"10.1002/open.70292","DOIUrl":"10.1002/open.70292","url":null,"abstract":"Chalcone-sulfonamide hybrids (12a–h) were synthesized via Claisen–Schmidt condensation in good yields (64%–83%) and confirmed by NMR spectroscopy. The compounds exhibited moderate to good antibacterial activity against Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus, Streptococcus pyogenes) bacteria, with inhibition zones of up to 14.7 mm at 10 mg/mL, lower than that of sulfamethoxazole but comparable to that of related hybrids. DPPH antioxidant evaluation revealed IC50 values of 5.2–11.8 μg/mL, with compounds 12e and 12c exhibiting the highest activity. Additionally, compound 12e had the strongest protein denaturation inhibition (IC50 = 29.89 µg/mL), while 12g and 12h showed superior anti-proteinase activity (IC50 = 115.6 and 112.2 µg/mL), outperforming diclofenac sodium. Molecular docking against DHPS (1AJ0, 1AD4), myeloperoxidase (1DNU), COX-2 (5IKR), and topoisomerase IIα (4FM9) showed strong binding affinities (−8.3 to −10.3 kcal/mol), supported by key hydrogen–bonding and hydrophobic interactions. SwissADME and ProTox II analyses indicate favorable drug-like properties, including Lipinski compliance, high GI absorption, no BBB penetration, and low predicted toxicity (LD50 > 6000 mg/kg). The hybrids presented here represent promising multifunctional leads with antibacterial, antioxidant, anti-inflammatory, and drug-like properties.","PeriodicalId":9831,"journal":{"name":"ChemistryOpen","volume":"15 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/open.70292","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148825267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanically Interlocked Molecules: A Supramolecular Computational Picture of Rotaxane-Based Switches, Shuttles, and Tristable Devices in Solution 机械互锁分子：溶液中基于轮烷的开关、穿梭器和可稳定器件的超分子计算图。

IF 3 4区化学

ChemistryOpen Pub Date : 2026-08-25 DOI: 10.1002/open.70291

Costantino Zazza

{"title":"Mechanically Interlocked Molecules: A Supramolecular Computational Picture of Rotaxane-Based Switches, Shuttles, and Tristable Devices in Solution","authors":"Costantino Zazza","doi":"10.1002/open.70291","DOIUrl":"10.1002/open.70291","url":null,"abstract":"This contribution highlights a coherent series of recent computational studies devoted to the theoretical characterization of mechanically interlocked molecules (MIMs)—specifically [2]rotaxane molecular shuttles and switches—in organic solvents. Combining density functional theory (DFT) and all-atoms molecular dynamics (MD) with the quantum theory of atoms in molecules (QTAIM) and the independent gradient model based on Hirshfeld partition (IGMH), a first-principles picture of the noncovalent and covalent interactions, repertoire that governs macrocycle translocation, metal-induced locking, and stimuli-responsive switching, has emerged. Distinct rotaxane platforms in different exercise conditions suggest that theoretical investigations can quantitatively reproduce and rationalize conformational shaping and spectroscopic observables, thereby providing a design roadmap for next-generation soft molecular machines of increasing complexity and functionalities. In this respect, the simulation scenario is further enriched by a self-consistent graphical visualization of both covalent and noncovalent interactions combining new computational strategies like the interaction region indicator (IRI) and the local electron energy density H(r) (GLED) descriptors over supramolecular assemblies of hundreds of atoms at the DFT cost.","PeriodicalId":9831,"journal":{"name":"ChemistryOpen","volume":"15 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting the ERK2 Signaling Pathway With Frog Skin-Derived Bioactive Peptides: Insights From Molecular Modeling, Molecular Dynamics, and Physicochemical Features 用青蛙皮肤衍生的生物活性肽靶向ERK2信号通路：来自分子建模、分子动力学和物理化学特征的见解。

IF 3 4区化学

ChemistryOpen Pub Date : 2026-08-24 DOI: 10.1002/open.70295

Nahlah Makki Almansour, Mahmoud M. H. Abdelhamid, Zahraa Alali, Mahmoud A. A. Ibrahim

{"title":"Targeting the ERK2 Signaling Pathway With Frog Skin-Derived Bioactive Peptides: Insights From Molecular Modeling, Molecular Dynamics, and Physicochemical Features","authors":"Nahlah Makki Almansour, Mahmoud M. H. Abdelhamid, Zahraa Alali, Mahmoud A. A. Ibrahim","doi":"10.1002/open.70295","DOIUrl":"10.1002/open.70295","url":null,"abstract":"ERK2 plays a vital function in promoting cell survival and proliferation by phosphorylating various substrates. ERK2 is a key druggable target owing to its function in uncontrolled cell proliferation and cancer, making selective ERK2 inhibitors essential for treating aggressive malignancies. Peptides are promising therapeutic agents with strong biological activity, and frog skin-derived peptides have shown notable anticancer potential. Seventeen curated frog skin-derived anticancer peptides were modeled and docked against the ERK2 D-recruitment site (DRS) using HADDOCK2.4 software. The predicted peptide-DRS complexes were introduced to molecular dynamics simulations (MDS), and their binding energies (ΔGbinding) were evaluated utilizing the MM/GBSA approach. Upon MM/GBSA//200 ns MDS, dermaseptin-B3, dermaseptin-PD-1, and ascaphin-8 showed better binding affinities against ERK2 DRS, with ΔGbinding values of −77.8, −74.1, and −56.7 kcal/mol, respectively, compared with the structurally resolved DRS-binding reference peptide KIM-MAP3 (ΔGbinding = −51.5 kcal/mol). Post-MD analyses, including binding energy per trajectory and RMSD analyses, affirmed the great stability of the identified peptides complexed with ERK2 DRS over 200 ns MDS. The predicted physicochemical features of the identified peptides indicated favorable functional potential. Collectively, these computational outcomes highlighted dermaseptin-B3, dermaseptin-PD-1, and ascaphin-8 as promising ERK2 DRS-binding candidates. Further experimental validation is required to confirm their functional inhibitory activity.","PeriodicalId":9831,"journal":{"name":"ChemistryOpen","volume":"15 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficient One-Pot Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles Using GO@SiO2@[(CH2)3Im][Cl] as a Novel Nanocomposite Under MW Irradiation 微波辐照下GO@SiO2@[(CH2)3Im][Cl]一锅高效合成1,2,4,5-四取代咪唑纳米复合材料

IF 3 4区化学

ChemistryOpen Pub Date : 2026-08-24 DOI: 10.1002/open.70281

Mohamed Abu Shuheil, Afaq Mahdi Ali, Mekkanti Manasa Rekha, Subhashree Ray, Talal Aziz Qassem, T. Krithiga, Renu Sharma, Prakhar Tomar, Reza Mohammadi

{"title":"Efficient One-Pot Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles Using GO@SiO2@[(CH2)3Im][Cl] as a Novel Nanocomposite Under MW Irradiation","authors":"Mohamed Abu Shuheil, Afaq Mahdi Ali, Mekkanti Manasa Rekha, Subhashree Ray, Talal Aziz Qassem, T. Krithiga, Renu Sharma, Prakhar Tomar, Reza Mohammadi","doi":"10.1002/open.70281","DOIUrl":"10.1002/open.70281","url":null,"abstract":"This study presents the development of a novel nanocomposite catalyst, GO@SiO2@[(CH2)3Im][Cl], for the efficient one-pot synthesis of 1,2,4,5-tetrasubstituted imidazoles under environmentally benign conditions. The catalyst design incorporates graphene oxide, silica, and an imidazolium-functionalized layer, creating a unique catalytic environment for the multicomponent reaction. Thorough characterization of the catalyst was performed using various analytical techniques, including FT-IR, XRD, SEM, TEM, and BET surface area analysis, confirming its successful synthesis and structural integrity. Under optimized solvent-free conditions and microwave irradiation, the reaction proceeds rapidly at room temperature, achieving excellent yields (90%–98%). Notably, the catalyst could be reused for up to seven consecutive cycles with minimal loss of activity and exhibits remarkable efficiency in promoting the four-component condensation of ammonium acetate, a substituted aniline, a substituted benzaldehyde, and benzil to form highly functionalized imidazoles in 18 examples. This sustainable approach represents a significant advancement over traditional methods, which often require harsh conditions, extended reaction times, and generate substantial waste. The use of microwave irradiation, coupled with a solvent-free protocol and room-temperature conditions, aligns perfectly with green chemistry principles. This work provides a practical and sustainable route to important heterocyclic scaffolds. It highlights the potential of rationally designed nanocomposite catalysts in developing more environmentally friendly synthetic processes for complex organic transformations.","PeriodicalId":9831,"journal":{"name":"ChemistryOpen","volume":"15 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An Effect of Preparation Temperature on the Structure and Reactivity of Supported Ni–Cu Bimetallic Nanoparticles in Benzyl Phenyl Ether Hydrogenolysis 制备温度对负载型Ni-Cu双金属纳米颗粒在苯基苯醚氢解中结构和反应活性的影响

IF 3 4区化学

ChemistryOpen Pub Date : 2026-08-21 DOI: 10.1002/open.70287

Raphaël Abolivier, Hans-Georg Eckhardt, Jimmy Muldoon, Michael Fay, James A. Sullivan

{"title":"An Effect of Preparation Temperature on the Structure and Reactivity of Supported Ni–Cu Bimetallic Nanoparticles in Benzyl Phenyl Ether Hydrogenolysis","authors":"Raphaël Abolivier, Hans-Georg Eckhardt, Jimmy Muldoon, Michael Fay, James A. Sullivan","doi":"10.1002/open.70287","DOIUrl":"https://doi.org/10.1002/open.70287","url":null,"abstract":"A set of four H-ZSM-5-supported Ni–Cu-containing materials with 5% Ni-1% Cu loadings was prepared. The effect of using different reduction protocols (non-reduced reference; H2 reduction at Tred.: 300; 400 and 500 °C) during the materials’ preparation was monitored to investigate the effect of this parameter on their microstructural features and their catalytic properties in a hydrogenolysis reaction. The variation of the reduction temperature has a direct effect on the composition and thus the separation of Ni atoms within the bimetallic nanoparticles and this in-turn affects their reactivities for the hydrogenolysis of benzyl phenyl ether (a lignin model compound). Alloy Cu/Ni-containing nanoparticles (confirmed by p-XRD) prepared by reduction at 400 °C containing relatively more separated Ni atoms (observed using transmission electron microscopy - energy dispersive x-ray spectroscopy (TEM-EDX)) were found to be more active in the reaction of interest than catalysts prepared using a reduction at 500 °C which had higher Ni contents (but lower Ni within particle separations).","PeriodicalId":9831,"journal":{"name":"ChemistryOpen","volume":"15 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/open.70287","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrative Phytochemical, Antioxidant, and NLRP3-Linked and Anti-Inflammatory Evaluation of Salvia balansae (Aurès Chemotype): Insights Into Its Safety and Therapeutic Potential 鼠尾草（aur<s:1>化学型）的综合植物化学、抗氧化、nlrp3相关和抗炎评价：其安全性和治疗潜力的见解

IF 3 4区化学

ChemistryOpen Pub Date : 2026-08-20 DOI: 10.1002/open.70280

Khadra Afaf Bendrihem, Messaoud Hachemi, Mohamed Aimene Mihoubi, Fares Mohamed Amine, Majid Sharifi-Rad, Dalal Houhou, Rahma Guemmaz, Khaled Kherraz, Azzeddine Zeraib, Assia Abdelmalek, Aicha Mouane, Nour Elhouda Ayeb, Chawki Bensuici, Maria Chikha, Kamel Nagaz, Ayomide Victor Atoki, Mohammed Messaoudi

{"title":"Integrative Phytochemical, Antioxidant, and NLRP3-Linked and Anti-Inflammatory Evaluation of Salvia balansae (Aurès Chemotype): Insights Into Its Safety and Therapeutic Potential","authors":"Khadra Afaf Bendrihem, Messaoud Hachemi, Mohamed Aimene Mihoubi, Fares Mohamed Amine, Majid Sharifi-Rad, Dalal Houhou, Rahma Guemmaz, Khaled Kherraz, Azzeddine Zeraib, Assia Abdelmalek, Aicha Mouane, Nour Elhouda Ayeb, Chawki Bensuici, Maria Chikha, Kamel Nagaz, Ayomide Victor Atoki, Mohammed Messaoudi","doi":"10.1002/open.70280","DOIUrl":"https://doi.org/10.1002/open.70280","url":null,"abstract":"Salvia balansae, an endemic Algerian species, remains poorly investigated despite the recognized medicinal importance of the Salvia genus. This study comprehensively evaluated its phytochemical composition, biological activities, and safety profile. Quantitative analyses revealed high levels of total phenolics, flavonoids, flavonols, condensed tannins, and triterpenoids, while LC–MS identified a distinctive Aurès-region chemotype enriched in luteolin, rosmarinic acid, and flavonoid glycosides. The extract demonstrated strong antioxidant activity in free radical-scavenging, metal-chelating, and reducing-power assays. Anti-inflammatory activity was confirmed by inhibition of protein denaturation in vitro and significant suppression of croton oil-induced ear edema and histopathological damage in vivo. Molecular docking predicted favorable binding of salvianolic acid, rutin, and apigenin-7-O-glucoside to NLRP3 inflammasome components, suggesting a potential mechanism underlying the observed anti-inflammatory effects. The extract also exhibited moderate inhibitory activity against cholinesterases and α-amylase, indicating possible neuroprotective and antidiabetic potential. Acute oral toxicity testing at 2000 mg/kg showed no mortality, major clinical signs of toxicity, or apparent organ damage, although repeated-dose studies are warranted. Collectively, these findings identify S. balansae as a polyphenol- and triterpenoid-rich species with considerable promise for pharmaceutical and nutraceutical applications.","PeriodicalId":9831,"journal":{"name":"ChemistryOpen","volume":"15 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/open.70280","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Review of the Therapeutic Potential of Stem Cell-Derived Nanocarriers to Treat Neurological Disorders 干细胞来源的纳米载体治疗神经系统疾病的潜力综述

IF 3 4区化学

ChemistryOpen Pub Date : 2026-08-20 DOI: 10.1002/open.202500425

Nnamdi Ikemefuna Okafor, Ahmed Abdelgader, Magdi Abobaker, Yahya E. Choonara

{"title":"A Review of the Therapeutic Potential of Stem Cell-Derived Nanocarriers to Treat Neurological Disorders","authors":"Nnamdi Ikemefuna Okafor, Ahmed Abdelgader, Magdi Abobaker, Yahya E. Choonara","doi":"10.1002/open.202500425","DOIUrl":"https://doi.org/10.1002/open.202500425","url":null,"abstract":"Neurological disorders (NDs) are characterized by substantial loss of specific neurons, with Alzheimer's and Parkinson's diseases being the most frequent NDs and nearly 99% of all “foreign substances” are prohibited from entering the brain by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (CFB). These barriers, while crucial for brain protection, pose significant challenges for drug delivery, as they restrict the entry of many therapeutic agents into the brain, and this represents the primary manifestation of the absence of pathogenesis-targeting therapeutics. With significant success across multiple cell transplantation research efforts, stem cell therapy has been utilized for decades to treat neurological disorders. They work by replacing injured or lost cells directly, releasing proliferation and neurotrophic factors through autocrine and paracrine actions, suppressing neurological inflammation, and activation of endogenous brain progenitor cells. Nanocarriers derived from stem cells represent an innovative and promising therapeutic strategy for combating neurological diseases, combining faculties of regeneration of stem cells with the precision of nanotechnology. These nanocarriers possess natural biocompatibility and can efficiently cross the BBB to transport the therapeutic agents directly to affected neural tissues, thereby promoting enhanced treatment efficacy while reducing off-target effects. However, key challenges remain in large-scale production, standardization, and long-term safety. Thus, this review has examined the potential applications of stem cell extracellular vesicle (EV)-nanocarriers, mainly exosomes and recent development in the treatment of neurological diseases.","PeriodicalId":9831,"journal":{"name":"ChemistryOpen","volume":"15 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/open.202500425","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of α,α-Difluoroketones via Zinc-Mediated Cross-Electrophile Coupling of gem-Difluoroenol Sulfonates and N-(acyloxy)phthalimides 锌介导的宝石-二氟醇磺酸盐和N-（酰基）邻苯二胺的交叉亲电偶联合成α，α-二氟酮

IF 3 4区化学

ChemistryOpen Pub Date : 2026-08-20 DOI: 10.1002/open.70285

Jing Zhao, Li Yang, Xiaohong Wang, Baojian Xiong, Xinmin Li, Huan Yang

引用次数: 0

Integrated In Silico Discovery of Thymoquinone Analogs Targeting the Keap1–Nrf2 Pathway for Amyotrophic Lateral Sclerosis Therapy 针对Keap1-Nrf2通路治疗肌萎缩性侧索硬化的百里醌类似物的集成芯片发现

IF 3 4区化学

ChemistryOpen Pub Date : 2026-08-18 DOI: 10.1002/open.70286

Jabir C. Nalicho, Petro E. Mabeyo, Andrew S. Paluch, Lucas Paul

{"title":"Integrated In Silico Discovery of Thymoquinone Analogs Targeting the Keap1–Nrf2 Pathway for Amyotrophic Lateral Sclerosis Therapy","authors":"Jabir C. Nalicho, Petro E. Mabeyo, Andrew S. Paluch, Lucas Paul","doi":"10.1002/open.70286","DOIUrl":"https://doi.org/10.1002/open.70286","url":null,"abstract":"Oxidative stress drives neuronal vulnerability in amyotrophic lateral sclerosis (ALS), making the Keap1–Nrf2 pathway a vital therapeutic target. While thymoquinone (TQ) modulates this axis, its efficacy is limited by low potency and poor drug-likeness. We utilized an integrated in silico workflow—including validated QSAR modeling (R2 = 0.68, Q2ext = 0.66), ADMET profiling, docking, 200 ns molecular dynamics, and MM–PBSA analysis—to identify improved TQ-derived Keap1 inhibitors. Screening 64 analogs prioritized three leads (CHEMBL3416163, CHEMBL4636830, and CHEMBL221598) with favorable safety and blood–brain barrier permeability. Docking and dynamics confirmed these analogs form stable interactions with Kelch domain hotspots. MM–PBSA calculations revealed significantly enhanced binding free energies (−75.10 to −93.79 kJ mol−1) compared to parent TQ (−21.05 kJ mol−1), driven primarily by van der Waals and hydrophobic forces. This study identifies structurally tractable TQ analogs with improved predicted potency and establishes a robust computational framework for neuroprotective discovery. The prioritized leads are compelling candidates for in vitro and in vivo validation as redox-modulating agents in ALS.","PeriodicalId":9831,"journal":{"name":"ChemistryOpen","volume":"15 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/open.70286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0