IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-20 DOI: 10.1002/cmdc.202500586

Juan Peris-Vicente, Devasish Bose, Rajendra-Pasad Pawar, Abhilasha Durgbanshi, Samuel Carda-Broch

{"title":"Micellar Liquid Chromatography Determination of Edoxaban in Oral Solid Dosage Forms: Theoretical Aspects and Validation.","authors":"Juan Peris-Vicente, Devasish Bose, Rajendra-Pasad Pawar, Abhilasha Durgbanshi, Samuel Carda-Broch","doi":"10.1002/cmdc.202500586","DOIUrl":"https://doi.org/10.1002/cmdc.202500586","url":null,"abstract":"A method based on micellar liquid chromatography has been developed to quantify edoxaban in oral solid dosage forms. Samples are dissolved in methanol and diluted in mobile phase up to nearly 5 mg L-1 and directly injected. The drug is resolved in less than 8 min using a C18 column and an isocratic mobile phase of 0.10 M sodium dodecyl sulfate -4%, v/v 1-butanol buffered at pH = 3 with a phosphate salt, running at 1 mL min- 1. The detection wavelength is 290 nm. The procedure is successfully validated by the guidelines of the International Conference on Harmonization. The calibration curve is linear (r2 > 0.999) over the interval 1-10 mg L-1. Trueness is 100.4-103.0% and precision < 1.7% and is finally applied to commercial tablets. The method is found to be quite sustainable by several quantitative assessed tools. The surfactant is found to be the primary contributor to the elution strength of the mobile phase and the partition constants of the equilibria involved in retention are determined. The method uses a low quantity of hazardous chemicals; is easy to conduct, safe, eco-friendly, and cost-effective, and offers a high sample throughput, thus suitable for routine analysis.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500586"},"PeriodicalIF":3.4,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel DAG-Lactone-Based Vav1 Inhibitors Show Anti-proliferative Activity in Pancreatic Cancer Models. 新型dag -内酯类Vav1抑制剂在胰腺癌模型中显示出抗增殖活性

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-20 DOI: 10.1002/cmdc.202500589

Ana Bellomo, Murat Toruner, Eleonora Elhalem, Megan L Peach, Lucía Gandolfi Donadío, Luciana Giordano, Tara L Hogenson, Martín E Fernandez-Zapico, María J Comin

{"title":"Novel DAG-Lactone-Based Vav1 Inhibitors Show Anti-proliferative Activity in Pancreatic Cancer Models.","authors":"Ana Bellomo, Murat Toruner, Eleonora Elhalem, Megan L Peach, Lucía Gandolfi Donadío, Luciana Giordano, Tara L Hogenson, Martín E Fernandez-Zapico, María J Comin","doi":"10.1002/cmdc.202500589","DOIUrl":"https://doi.org/10.1002/cmdc.202500589","url":null,"abstract":"Targeting C1 domains is a promising strategy for modulating the activity of signaling proteins driving tumor growth and progression. While most small molecules developed to date have focused on typical C1 domains, the development of regulators targeting atypical C1 domains remains under-explored. Herein, we describe the design and synthesis of novel cationic diacylglycerol DAG-lactones to efficiently interact with the negatively charged residues present in the atypical C1 domain of Vav1, a guanine nucleotide exchange factor playing a critical role in tumor development, including pancreatic cancer. We evaluated the therapeutic potential of this new family of compounds using models from this dismal condition where Vav1 is aberrantly expressed. Treatment of cultured pancreatic tumor cells with sn-1 cationic DAG-lactones inhibited proliferation of Vav1-expressing cells while Vav1-negative cells showed no response. Additionally, we demonstrated that these compounds inhibited growth of patient-derived organoids models of pancreatic cancer. These findings underscore the translational value of these cationic DAG-lactones for pancreatic cancer patients expressing Vav1 and serve as foundation for future approaches targeting atypical C1 domain-containing signaling proteins.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500589"},"PeriodicalIF":3.4,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent Progress on Topical Drug Therapy for Corneal Neovascularization. 角膜新生血管外用药物治疗的最新进展。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-16 DOI: 10.1002/cmdc.202500366

Xin-Can Huang, Guo-Yang Xu, Pei-Pei Yang, Lei Wang, Hao Wang, Ying Hu

{"title":"Recent Progress on Topical Drug Therapy for Corneal Neovascularization.","authors":"Xin-Can Huang, Guo-Yang Xu, Pei-Pei Yang, Lei Wang, Hao Wang, Ying Hu","doi":"10.1002/cmdc.202500366","DOIUrl":"https://doi.org/10.1002/cmdc.202500366","url":null,"abstract":"The cornea is a crucial refractive medium in the visual system, characterized by its avascular and transparent nature under physiological conditions. Pathological factors such as ocular trauma and inflammation can induce the formation of new capillaries from the limbal vascular network, leading to corneal neovascularization (CNV). With an associated blindness rate as high as 12%, CNV has become a significant challenge in ophthalmology. Current treatment strategies for CNV primarily include drug therapy such as anti-inflammatory and antiangiogenic agents, as well as surgical procedures like laser photocoagulation. These approaches are often limited by invasive procedures, suboptimal efficacy, and other constraints. Therefore, developing effective, safe, and convenient therapeutic options has become a critical research focus. Due to structural barriers of the ocular surface, the bioavailability of conventional eye drops is limited to ≈1%-5%, significantly restricting therapeutic efficacy. In recent years, researchers have been actively optimizing drug delivery systems using nanotechnology, hydrogels, and other advanced techniques to prolong ocular surface retention time, improve corneal penetration, and enhance drug release properties. This review summarizes recent advances in topical drug therapy for CNV, focusing on its pathogenesis, therapeutic agents, and delivery strategies, as well as approaches to enhance the bioavailability of topical treatments.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500366"},"PeriodicalIF":3.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploration of New Pyrazole-Hydrazone-Benzenesulfonamide Conjugates as Potent Mycobacterial Carbonic Anhydrase Inhibitors: Design, Synthesis, and Biological Evaluation. 新型吡唑-腙-苯磺酰胺偶联物作为分枝杆菌碳酸酐酶抑制剂的探索：设计、合成和生物学评价。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-16 DOI: 10.1002/cmdc.202500633

Pardeep Kumar, Anuradha Singampalli, Rani Bandela, Sri Mounika Bellapukonda, Laxma Naik Korra, Ramakrishna Kodi, Subhendu Ghosh, Aman Dalal, Puja Kumari Agnivesh, Ankita Devi, Srinivas Nanduri, Nitin Pal Kalia, Niccolò Paoletti, Alessandro Bonardi, Paola Gratteri, Claudiu T Supuran, Venkata Madhavi Yaddanapudi

{"title":"Exploration of New Pyrazole-Hydrazone-Benzenesulfonamide Conjugates as Potent Mycobacterial Carbonic Anhydrase Inhibitors: Design, Synthesis, and Biological Evaluation.","authors":"Pardeep Kumar, Anuradha Singampalli, Rani Bandela, Sri Mounika Bellapukonda, Laxma Naik Korra, Ramakrishna Kodi, Subhendu Ghosh, Aman Dalal, Puja Kumari Agnivesh, Ankita Devi, Srinivas Nanduri, Nitin Pal Kalia, Niccolò Paoletti, Alessandro Bonardi, Paola Gratteri, Claudiu T Supuran, Venkata Madhavi Yaddanapudi","doi":"10.1002/cmdc.202500633","DOIUrl":"https://doi.org/10.1002/cmdc.202500633","url":null,"abstract":"The growing threat of multidrug-resistant tuberculosis highlights the need for new agents with alternative mechanisms of action. Herein, a series of pyrazole-sulfonamide derivatives are synthesized and evaluated for inhibition of Mycobacterium tuberculosis β-carbonic anhydrases (MtCA 1 and MtCA 3). N-substituted analogues (6a-6i) are inactive, while compounds bearing a free sulfonamide group (SO2NH2) (5a-5s) exhibit potent inhibitory activity, with Ki values of 0.2154-0.7542 µM for MtCA 1 and 0.0548-0.3241 µM for MtCA 3. Molecular docking studies support their binding interactions and selectivity. Antitubercular screening of all synthesized compounds reveals minimum inhibitory concentration (MIC) values in the range of 4-128 µg mL-1. Among them, compound 5p emerges as the most potent derivative, with a Ki of 0.07 µM against MtCA 3 and an MIC of 8 µg mL-1, outperforming the reference inhibitor acetazolamide. It exhibits no cytotoxicity in THP-1 cells, showing no toxicity against human cell lines, and demonstrates a favorable selectivity index. Furthermore, compound 5p retains activity against rifampicin-resistant M. tuberculosis. In silico ADMET predictions indicate acceptable pharmacokinetic and safety profiles. These findings suggest that compound 5p is a promising lead for the development of novel antitubercular agents, potentially acting through MtCA inhibition.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500633"},"PeriodicalIF":3.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigations on Antiproliferative Potential of Thiosemicarbazone Zn(II) Complexes: Design, Synthesis, and Density Functional Theory Studies on Structural Parameters. 硫代氨基脲锌（II）配合物抗增殖潜能的研究：设计、合成及结构参数的密度泛函理论研究。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-16 DOI: 10.1002/cmdc.202500545

Shivendra K Pandey, Abhishek Kumar, Sushil K Gupta, Ajay Kumar, Manoj K Bharty

{"title":"Investigations on Antiproliferative Potential of Thiosemicarbazone Zn(II) Complexes: Design, Synthesis, and Density Functional Theory Studies on Structural Parameters.","authors":"Shivendra K Pandey, Abhishek Kumar, Sushil K Gupta, Ajay Kumar, Manoj K Bharty","doi":"10.1002/cmdc.202500545","DOIUrl":"https://doi.org/10.1002/cmdc.202500545","url":null,"abstract":"Zinc complexes have promising possibilities as medicines since they have better efficacy and lower toxicity. Herein, two ligands are synthesized based on hydrazine-1-carbothioamide with substituents having different electronic nature {nitro (HNPhHCT) and methoxy (HMoPhHCT)} and their respective Zn(II) complexes {[Zn(NPhHCT)2] and [Zn(MoPhHCT)2]}. They have been fully characterized via several spectroscopic techniques (IR, NMR, HRMS, UV-Vis studies) and DFT studies. In addition, ligands and their respective complexes are screened for their antiproliferative activity against three different cancer cell lines, namely HuT-78 (T-cell lymphoma), DL (Dalton's lymphoma), and MCF-7 (Breast cancer) cell lines. Among the two complexes, [Zn(MoPhHCT)2] is found to be most cytotoxic on all three cancer cell lines. In HuT-78 cells, [Zn(MoPhHCT)2] exhibited IC50 value at ≈4 µM. Further, glucose and ROS estimation assays suggested that [Zn(MoPhHCT)2] shows antiproliferative activity against T lymphoma cells by inhibiting their glycolytic activity and apoptosis induction by increasing ROS production. A molecular docking study is performed against an antiapoptotic protein, BCL2 (PDB: 2O2F), that confirms its inhibitory response with a binding score of -8.34 kcal mol-1. Further, the expression of BCL2 at the protein level is found to be significantly inhibited in response to treatment with [Zn(MoPhHCT)2], as evident by the Western blot analysis results.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500545"},"PeriodicalIF":3.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the Potential of a New β-Cyclodextrin-Suxibuzone Conjugate in Proteasome Regulation. 揭示新的β-环糊精-苏西布酮偶联物在蛋白酶体调控中的潜力。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-16 DOI: 10.1002/cmdc.202500401

Noemi Bognanni, Stefania Zimbone, Maria Laura Giuffrida, Giuseppe Di Natale, Danilo Milardi, Graziella Vecchio, Valeria Lanza

{"title":"Unveiling the Potential of a New β-Cyclodextrin-Suxibuzone Conjugate in Proteasome Regulation.","authors":"Noemi Bognanni, Stefania Zimbone, Maria Laura Giuffrida, Giuseppe Di Natale, Danilo Milardi, Graziella Vecchio, Valeria Lanza","doi":"10.1002/cmdc.202500401","DOIUrl":"https://doi.org/10.1002/cmdc.202500401","url":null,"abstract":"The proteasome is a central component of the cellular machinery responsible for degrading misfolded or damaged proteins, thereby maintaining protein homeostasis. Dysregulation of proteasome activity has been implicated in various diseases, including neurodegenerative disorders and cancer. In this article, a new β-cyclodextrin conjugate of suxibuzone (SB-CD) is designed and its proteasome activity on purified human 20S core particle and in differentiated human neuroblastoma SH-SY5Y cells (dSHSY5Y) is investigated. This conjugate enhances the proteolytic activity of the 20S proteasome in a dose-dependent manner, with an increase observed at concentrations as low as 5 µM. The EC50 values for SB-CD are determined to be 0.6 ± 0.1 µM for chymotrypsin-like activity and 1.1 ± 0.3 µM for trypsin-like activity, indicating higher efficacy compared to suxibuzone alone. In dSH-SY5Y cells, a decrease in the accumulation of ubiquitinated proteins is observed, consistent with the activation of the proteasome. High-resolution electrospray ionization mass spectrometry investigations confirmed the internalization of SB-CD in cells and verified the stability of the conjugate in response to cellular protease effects, after incubation for up to 24 h. These promising results suggest that the new conjugate is an effective enhancer of proteasome activity, holding significant promise for therapeutic applications targeting proteasome-related pathologies.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500401"},"PeriodicalIF":3.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design and Evaluation of Sticky End-Type Bivalent DNA Aptamers Containing M08s-1 as Anticoagulant Agents. 含有M08s-1的粘端型二价DNA适体抗凝剂的设计与评价。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-16 DOI: 10.1002/cmdc.202500688

Maasa Yokomori, Mizuki Murasawa, Muneyuki Matsuo, Masanobu Nagano, Keitaro Yoshimoto

{"title":"Design and Evaluation of Sticky End-Type Bivalent DNA Aptamers Containing M08s-1 as Anticoagulant Agents.","authors":"Maasa Yokomori, Mizuki Murasawa, Muneyuki Matsuo, Masanobu Nagano, Keitaro Yoshimoto","doi":"10.1002/cmdc.202500688","DOIUrl":"https://doi.org/10.1002/cmdc.202500688","url":null,"abstract":"Aptamer is a promising therapeutic modality, offering strong target affinity and target versatility. In the previous studies, DNA aptamers with potent thrombin inhibitory activity, M08s-1 and its bivalent derivatives, have been developed as novel anticoagulant agents. Among them, the heterobivalent aptamer Pse08-29 exhibits the most potent ex vivo anticoagulant activity, surpassing the approved drug argatroban. However, its long oligonucleotide chains composed of 106 nucleotides may hinder its drug development due to limited chemical synthetic efficiency. Here, a segmented form of Pse08-29 composed of two DNA strands, assembled via a sticky end-type strategy, is developed. The cleavage positions and optimal linker lengths are studied based on the anticoagulant activity and structural stability, revealing that a few cleavage sites within the duplex linker region are acceptable without losing the activity. Surprisingly, one of such aptamers, Stick08-29(19-B), shows the significantly enhanced serum stability compared to Pse08-29, despite the two nick-like sites existing. Finally, selected bivalent aptamers, consisting of two split DNA strands (<65 mer), exhibit the high anticoagulant activity as well as Pse08-29. This highlights not only efficient nucleobase reduction with preserved function but also a new design strategy for bivalent aptamers.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500688"},"PeriodicalIF":3.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Natural Staurosporine Derivatives with Fluorescence for Cancer Theranostics. 荧光天然Staurosporine衍生物在癌症治疗中的应用。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-16 DOI: 10.1002/cmdc.202500629

Kualiang Li, Wei Liu, Tong Wu, Yongbo Wei, Ying Liu, Jingming Zhou, Li Chen, Jian Zhou, Yusheng Lu, Haipeng Xu, Lijun Xie

{"title":"Natural Staurosporine Derivatives with Fluorescence for Cancer Theranostics.","authors":"Kualiang Li, Wei Liu, Tong Wu, Yongbo Wei, Ying Liu, Jingming Zhou, Li Chen, Jian Zhou, Yusheng Lu, Haipeng Xu, Lijun Xie","doi":"10.1002/cmdc.202500629","DOIUrl":"https://doi.org/10.1002/cmdc.202500629","url":null,"abstract":"In recent years, developing effective theranostic agents for precise cancer treatment has been one of the most prevalent strategies. Herein, three staurosporine derivatives, MCY-STS, ECY-STS, and ICY-STS, synthesized through minor modifications of natural staurosporine, are reported. These derivatives not only exhibit attractive fluorescence properties, including solvatochromism and dual-state (solution and solid) emission, but also demonstrate potent protein kinase C inhibitory activity and anticancer effects against NCI-N87, MCF-7, and SK-OV-3 cell lines. Theoretical calculation analyses, including density functional theory calculations, molecular docking, and molecular dynamics simulations, are employed to elucidate their protein-ligand interactions and luminescence mechanisms. Further investigations reveal that ECY-STS significantly inhibits tumor growth while illuminating tumor tissues for therapy visualization. Collectively, these modified fluorescent staurosporine derivatives, particularly ECY-STS, represent promising theranostic agents that provide a novel strategy for cancer imaging and treatment in humans.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500629"},"PeriodicalIF":3.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Front Cover: Development of a Tumor Microenvironment-Responsive Co(III)-Chrysin Prodrug: Synthesis, Activation Profiling, and In Vitro Antineoplastic Evaluation (ChemMedChem 20/2025) 封面：肿瘤微环境响应型Co(III)-Chrysin前药的开发：合成、激活分析和体外抗肿瘤评价（ChemMedChem 20/2025）

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-16 DOI: 10.1002/cmdc.70068

Prakash Shukla, Krishna Kanta Choudhury, Kajol, Subhrata Behera, Janhabi Panigrahy, Rakesh Kumar Pathak

引用次数: 0

Synthesis and Biological Activity for 1,3,4-Thiadiazole-2-Iminothiazolidin-4-Ones: Antidiabetic and Anti-Alzheimer Activity. 1,3,4-噻二唑-2-亚氨基噻唑烷-4- ones的合成及其生物活性：抗糖尿病和抗阿尔茨海默病活性

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-16 DOI: 10.1002/cmdc.202500620

Vu Ngoc Toan, Nguyen Dinh Thanh, Nguyen Minh Tri

{"title":"Synthesis and Biological Activity for 1,3,4-Thiadiazole-2-Iminothiazolidin-4-Ones: Antidiabetic and Anti-Alzheimer Activity.","authors":"Vu Ngoc Toan, Nguyen Dinh Thanh, Nguyen Minh Tri","doi":"10.1002/cmdc.202500620","DOIUrl":"https://doi.org/10.1002/cmdc.202500620","url":null,"abstract":"A series of 2-iminothiazolidin-4-one-1,3,4-thiazole hybrids 7a-l are synthesized and screened for their inhibitory activities against responsible enzymes in type 2 diabetes mellitus (T2DM) and Alzheimer's diseases. Among the compounds with potential inhibitory activity, several 2-iminothiazolidin-4-ones exhibit the strongest inhibitory activity against the screened enzymes, including 7c (IC50 = 6.12 ± 0.11 µM, for α-amylase), 7e (IC50 = 6.78 ± 0.15 µM, for α-glucosidase), 7k (IC50 = 1.82 ± 0.04 µM, for DPP-4), 7f (IC50 = 2.21 ± 0.02 µM, for PTP1B), 7h (IC50 = 0.06 ± 0.01 nM, for AChE), 7j (IC50 = 0.03 ± 0.01 nM, for BChE, and IC50 = 0.32 ± 0.01 nM, for MAO-A), and 7l (IC50 = 0.02 ± 0.01 nM, for MAO-B). Compound 7j exhibits the strongest inhibitory activity for both BChE and MAO-A. Compounds with short-chain alkyl groups (2-4 carbon atoms) have the strongest inhibitory activity against the enzymes responsible in T2DM, with the exception of 7k (with 6-carbon atom chain), whereas the long-chain alkyl groups (with 5-7 carbon atom chains) have the strongest inhibitory activity against the enzymes responsible in Alzheimer's disease. These compounds also exhibit the high antiglycation and antioxidant activity in DPPH and ABTS•+ scavenging assays. They are noncytotoxic for WI-38 cell line with IC50 > 76 μM.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500620"},"PeriodicalIF":3.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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