ChemMedChem最新文献_第2页

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

Monitoring Apoptotic Activity of Silver(I) Metallodrugs Containing Mefenamic Acid and Mitochondriotropic Agents in Artificial Breast Tumor Tissues. 人工乳腺肿瘤组织中含甲氧胺酸银金属药物及线粒体促凋亡活性的监测

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-16 DOI: 10.1002/cmdc.202500414

Christina N Banti, Sotiris K Hadjikakou

{"title":"Monitoring Apoptotic Activity of Silver(I) Metallodrugs Containing Mefenamic Acid and Mitochondriotropic Agents in Artificial Breast Tumor Tissues.","authors":"Christina N Banti, Sotiris K Hadjikakou","doi":"10.1002/cmdc.202500414","DOIUrl":"https://doi.org/10.1002/cmdc.202500414","url":null,"abstract":"The anticancer potential of silver(I) metallodrugs incorporating mefenamic acid and mitochondriotropic agents in 3D spheroid models of hormone-dependent breast cancer cells (MCF-7) is investigated within this work. The compounds, previously evaluated in 2D cultures, demonstrated potent antiproliferative activity with IC50 values ranging from 1.01 to 5.20 μM, significantly outperforming cisplatin. Here, 3D spheroids are employed to simulate the tumor microenvironment, assessing drug efficacy through morphological changes and apoptosis rates. Compounds 1-4 exhibited dose- and time-dependent reductions in spheroid compactness and sphericity, with compound 2 achieving complete loss of compactness (0%) and sphericity (2%) at 10 μM after 48 h. Apoptotic activity is also significantly higher in 3D spheroids treated with these compounds with respect to their control (25.8%-41.4%), in contrast to cisplatin (24.4%) and untreated cells (8.0%). The results validate the superior efficacy of silver(I) complexes in disrupting tumor integrity and inducing apoptosis. This study underscores the potential of 3D spheroid models for preclinical evaluation and highlights silver(I) metallodrugs as promising candidates for breast cancer therapy. Future research should focus on in vivo validation to further explore their therapeutic applications.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500414"},"PeriodicalIF":3.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306511","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

Exploring Indole-1,3,4-Thiadiazole Schiff Base Derivatives as Anticancer Agents: Design, Synthesis, In Vitro and In Silico Evaluation. 吲哚-1,3,4-噻二唑希夫碱衍生物抗癌作用的研究：设计、合成、体外及硅评价

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-10 DOI: 10.1002/cmdc.202500231

Umadevi Etikyala, Rajkumar Reddyrajula, Udaya Kumar Dalimba, Premalatha Kokku, Vijjulatha Manga

{"title":"Exploring Indole-1,3,4-Thiadiazole Schiff Base Derivatives as Anticancer Agents: Design, Synthesis, In Vitro and In Silico Evaluation.","authors":"Umadevi Etikyala, Rajkumar Reddyrajula, Udaya Kumar Dalimba, Premalatha Kokku, Vijjulatha Manga","doi":"10.1002/cmdc.202500231","DOIUrl":"https://doi.org/10.1002/cmdc.202500231","url":null,"abstract":"Cancer remains a major global health challenge, with resistance to existing therapeutic regimens underscoring the development of novel agents with improved efficacy and reduced toxicity. The indole and 1,3,4-thiadiazole scaffolds are distinguished for their broad-spectrum bioactivities, including anticancer properties. In this study, the synthesis and biological evaluation of a new series of indole-1,3,4-thiadiazole Schiff bases (U1-U31) designed to enhance anticancer efficacy is explored. In vitro evaluation demonstrates potent and selective cytotoxicity of several compounds, particularly U19 and U24, against multiple cancer cell lines, with minimal toxicity to normal cells. Molecular docking and density functional theory studies demonstrate that these hybrid compounds effectively occupy the ATP-binding sites of Pi3K and Akt proteins, exhibiting notable binding interactions comparable to the respective standard inhibitors. In addition, molecular dynamics simulation is performed to understand the conformational changes of the protein-ligand complex. Overall, the findings indicate that these novel indole-1,3,4-thiadiazole derivatives have selective inhibitory potency, making them promising leads for further anticancer drug development.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500231"},"PeriodicalIF":3.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273132","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

Potent Antisickling Furaldehyde Analogs for Acute Sickle Cell Therapy: Enhanced Efficacy and Intravenous Formulation Potential. 有效抗镰状细胞的呋喃醛类似物急性镰状细胞治疗：提高疗效和静脉制剂的潜力。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-10 DOI: 10.1002/cmdc.202500507

Abdelsattar M Omar, Moustafa E El-Araby, Tarek A Ahmed, Akua K Donkor, Albert Opare, Mohini S Ghatge, Anfal S Aljahdali, Rana T Alhashimi, Trevohn N Robinson, Benita Balogun, Mariana Macias, Salma Roland, Yan Zhang, Faik N Musayev, Osheiza Abdulmalik, Martin K Safo

{"title":"Potent Antisickling Furaldehyde Analogs for Acute Sickle Cell Therapy: Enhanced Efficacy and Intravenous Formulation Potential.","authors":"Abdelsattar M Omar, Moustafa E El-Araby, Tarek A Ahmed, Akua K Donkor, Albert Opare, Mohini S Ghatge, Anfal S Aljahdali, Rana T Alhashimi, Trevohn N Robinson, Benita Balogun, Mariana Macias, Salma Roland, Yan Zhang, Faik N Musayev, Osheiza Abdulmalik, Martin K Safo","doi":"10.1002/cmdc.202500507","DOIUrl":"https://doi.org/10.1002/cmdc.202500507","url":null,"abstract":"Sickle cell disease (SCD) is a debilitating inherited blood disorder characterized by acute crises that require immediate intervention. Aromatic aldehydes that increase hemoglobin (Hb) oxygen affinity (e.g., 5-HMF) can prevent hypoxia-induced erythrocyte sickling, but clinical efforts have been hindered by insufficient potency or poor pharmacokinetics. Herein, analogs of 5-HMF (MMA-500 series of compounds) are reported to retain 5-HMF positive physicochemical and pharmacodynamic properties, including safety, solubility, and relatively short duration of action that are essential for their acute use. Two analogs, MMA503 and MMA509, demonstrate over 3.3-fold greater in vitro antisickling activity than 5-HMF. This potency is evidenced by significantly enhanced Hb adduct formation, increased oxygen affinity, and robust inhibition of red blood cell sickling in sickle blood assays. X-ray crystallography further elucidates the Hb binding interactions underlying their potency at the molecular level. MMA509 emerges as a lead candidate and is advanced to formulation studies. An IV formulation of MMA509 in 40% polyethylene glycol 400 achieves ≈13.5 mg mL-1 solubility, enabling rapid attainment of therapeutic drug levels. The potent pharmacologic profile of MMA509, combined with its successful parenteral formulation, highlights its promise as a fast-acting therapeutic for acute SCD crises as a result of rapid onset expected from IV dosing.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500507"},"PeriodicalIF":3.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273141","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

A Dual-Emissive Lanthanide Organic light-emitting diode for Single-Pixel Pulse Oximetry: From Molecular Design to Device-Level Integration. 用于单像素脉冲氧饱和度测量的双发射镧系有机发光二极管：从分子设计到器件级集成。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-10 DOI: 10.1002/cmdc.202500465

Andrey I Kornikov, Makarii I Kozlov, Andrey A Vashchenko, Andrey A Poyarkov, Alexander S Goloveshkin, Egor V Latipov, Leonid S Lepnev, Valentina V Utochnikova

{"title":"A Dual-Emissive Lanthanide Organic light-emitting diode for Single-Pixel Pulse Oximetry: From Molecular Design to Device-Level Integration.","authors":"Andrey I Kornikov, Makarii I Kozlov, Andrey A Vashchenko, Andrey A Poyarkov, Alexander S Goloveshkin, Egor V Latipov, Leonid S Lepnev, Valentina V Utochnikova","doi":"10.1002/cmdc.202500465","DOIUrl":"https://doi.org/10.1002/cmdc.202500465","url":null,"abstract":"Organic light-emitting diodes (OLEDs) with dual emission in the red and near-infrared regions offer a breakthrough opportunity for simplifying pulse oximetry technology. Here, a new class of bimetallic complexes Eu0.1Yb0.9(L)3Q (L = β-diketonates; Q = neutral ligands) with simultaneous emission at 612 and 978 nm has been reported, optimized for solution-processed OLEDs. A device based on Eu0.1Yb0.9(dbm)3thiadiazolophenanthroline (TDZP) exhibits the highest electroluminescence intensity in both spectral ranges and is employed as a single-pixel light source in a custom-built pulse oximeter prototype. The prototype demonstrates real-time measurement of heart rate and blood oxygen saturation in full agreement with commercial devices. This is the first demonstration of a fully functional OLED-based oximeter relying on dual-emissive lanthanide complexes. This results pave the way for next-generation wearable biomedical sensors using advanced emissive materials and simplified device architectures.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500465"},"PeriodicalIF":3.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273167","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

Enhancing Stability and Entrapment Efficiency of Liposome-Coated Mesoporous Silica Nanocarriers Using Polyoxyethylene Alkyl Ether as a Polyethylene Glycol Anchoring Agent. 以聚氧乙烯烷基醚为聚乙二醇锚定剂，提高脂质体包覆介孔二氧化硅纳米载体的稳定性和包封效率。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-07 DOI: 10.1002/cmdc.202500223

Tien-Dung Nguyen-Dinh, Ngoc Hoi Nguyen, Tan Phat Nguyen, Ngoc Thuy Trang Le, Dai Hai Nguyen

{"title":"Enhancing Stability and Entrapment Efficiency of Liposome-Coated Mesoporous Silica Nanocarriers Using Polyoxyethylene Alkyl Ether as a Polyethylene Glycol Anchoring Agent.","authors":"Tien-Dung Nguyen-Dinh, Ngoc Hoi Nguyen, Tan Phat Nguyen, Ngoc Thuy Trang Le, Dai Hai Nguyen","doi":"10.1002/cmdc.202500223","DOIUrl":"https://doi.org/10.1002/cmdc.202500223","url":null,"abstract":"The development of a phospholipid bilayer coating on the nanoparticle surface, particularly mesoporous nanosilica (MSN), has recently emerged as a promising strategy in drug delivery systems. However, the strong interactions of the phospholipid bilayer promote the adsorption of plasma proteins onto nanocarriers, leading to physicochemical instability and undesired aggregation. This study explores the use of polyoxyethylene alkyl ether (Brij), a PEG-based surfactant, to enhance the stability of phospholipid bilayer-coated MSN in serum environments. Initially, Brij-coated liposome (LB), a type of phospholipid-based nanoparticles, is synthesized via the thin film hydration method. The LB is subsequently immobilized onto the MSN surface to form Brij-coated MSN-liposome nanoparticles (MLB). The physicochemical properties and morphology of MLB are characterized through Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, Brunauer-Emmett-Teller, scanning electron microscopy, transmission electron microscopy, and dynamic light scattering. The Brij-coated MLB exhibited significantly improved stability in serum environments compared to MSN coated with an unmodified phospholipid bilayer. Furthermore, the influence of Brij on the loading capacity and release behavior of a poorly water-soluble drug was assessed using quercetin as a model drug. Biocompatibility assessments demonstrated that MLB exhibited low cytotoxicity when tested on HeLa cells, indicating its potential for biomedical applications.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500223"},"PeriodicalIF":3.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243366","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

API-ILs Ionic Adducts: Solubility and Surface Activity Properties-En Route to New Paradigm in Drug Development. api - il离子加合物：溶解度和表面活性特性——在药物开发的新范式之路上。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-07 DOI: 10.1002/cmdc.202500404

Janusz Nowicki, Marian M Zgoda, Marcin Muszyński, Jyri-Pekka Mikkola, Michał Kołodziejczyk

{"title":"API-ILs Ionic Adducts: Solubility and Surface Activity Properties-En Route to New Paradigm in Drug Development.","authors":"Janusz Nowicki, Marian M Zgoda, Marcin Muszyński, Jyri-Pekka Mikkola, Michał Kołodziejczyk","doi":"10.1002/cmdc.202500404","DOIUrl":"https://doi.org/10.1002/cmdc.202500404","url":null,"abstract":"Two novel, structurally different perfluoroalkyl ionic liquids with bicyclic guanidinium cation have been synthesized and applied as a surfactant component for selected active pharmaceutical ingredients (APIs). The addition of perfluoroalkyl ionic liquid to hydrophobic APIs significantly improves their solubility. One of the key and characteristic properties of guanidine derivatives is their strong ability to chemisorb protons (proton affinity). This property enables them to form stable ionic-type aggregates (adducts) with selected hydrophobic APIs containing carboxylic groups. Therefore, these new compounds are, in fact, API-IL ionic adducts formed as hydrogen bond donor-acceptor systems. The obtained adducts are characterized by significantly better solubility than the initial APIs. The presence of perfluoroalkyl chains with unique surface-active properties enables to obtain a solubility of new adducts to reach level sufficient for typical ophthalmic preparations. (e.g., eye drops or lens care). The ionic API-IL adducts obtained in the described studies can be considered as examples of a new class of active derivatives with pharmaceutical potential.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500404"},"PeriodicalIF":3.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243343","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

Delivery of a GPX4 Inhibitor by SN38 Prodrug Nanoassemblies for Amplified Antitumor Efficacy Based on Ferroptotic Chemotherapy. 通过SN38前药纳米组件递送GPX4抑制剂以增强基于铁致化疗的抗肿瘤效果。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-07 DOI: 10.1002/cmdc.202500667

Lin Li, Yanyan Wu, Weiwei Wang, Kejing Wang, Lin Chen

{"title":"Delivery of a GPX4 Inhibitor by SN38 Prodrug Nanoassemblies for Amplified Antitumor Efficacy Based on Ferroptotic Chemotherapy.","authors":"Lin Li, Yanyan Wu, Weiwei Wang, Kejing Wang, Lin Chen","doi":"10.1002/cmdc.202500667","DOIUrl":"https://doi.org/10.1002/cmdc.202500667","url":null,"abstract":"Prodrug-based self-assembled nanoassemblies, with carrier-free structures and high drug loading, are garnering attention for chemotherapy. Additionally, the synergistic effects of prodrug nanoassemblies combined with multiple cell death pathways deserve further exploration. Ferroptosis has emerged as a powerful nonapoptotic cell death modality, showing significant potential for tumor inhibition. Therefore, prodrug nanoassemblies combined with ferroptosis inducers may achieve amplified antitumor efficacy. Herein, a GPX4 inhibitor (ML210)-loaded SN38 prodrug nanoparticle system is developed to enhance antitumor efficacy via ferroptotic-chemotherapy synergy. In this system, SN38 is conjugated to 1-octadecanol by a disulfide linkage to construct the self-assembly prodrug. DSPE-PEG2k is applied to stabilize nanoassemblies. It is proven that ML210 is successfully encapsulated into the SN38 prodrug nanoassemblies by the one-step precipitation method. Both prodrug nanoassemblies exhibit good stability and a GSH-responsive release profile. Furthermore, ML210-loaded nanoassemblies show stronger cytotoxicity, greater proliferation inhibition, and obvious ferroptosis activation. In the CT26 mouse model, ML210-loaded prodrug nanoassemblies demonstrated superior antitumor effects. The strategy-using prodrug as \"carriers\" for ferroptosis inducers-offers a promising approach for synergistic antitumor therapy.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500667"},"PeriodicalIF":3.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243326","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

Coumarin-Caged Nanoparticle for Light-Driven Surface Modification. 香豆素笼纳米粒子光驱动表面修饰。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-07 DOI: 10.1002/cmdc.202500636

Jan Birringer, Johannes Konrad, Stephan Melchner, Marius Remmert, Achim Goepferich

{"title":"Coumarin-Caged Nanoparticle for Light-Driven Surface Modification.","authors":"Jan Birringer, Johannes Konrad, Stephan Melchner, Marius Remmert, Achim Goepferich","doi":"10.1002/cmdc.202500636","DOIUrl":"https://doi.org/10.1002/cmdc.202500636","url":null,"abstract":"Photo-labile protecting groups (PPG) allow for the selective activation of an originally caged moiety by light exposure at a specific wavelength. Incorporation of PPG in nanoparticles (NPs) enables precise spatiotemporal control over NPs surface properties. Thus, physicochemical and biological properties of NPs can be modified even after administration in a biological environment. In this study, this mechanism is used to control the cell uptake of NPs. To this end, polymeric core-shell NPs are used composed of poly(D, L-lactide-co-glycolide) and a poly(ethylene glycol)-b-poly(D, L-lactide) block copolymer, modified with positively charged cell-penetrating peptide (CPP). Surface charge of CPP-NPs (+23.50 mV), measured as zetapotential, is effectively diminished by the attachment of coumarin-derived PPG to CPP (+12.50 mV), resulting in reduced cell uptake. Upon light irradiation with light-emitting diode (λ = 365 nm) the PPG is cleaved, restoring the zetapotential (+24.67 mV) and triggering an enhanced cell uptake. This opens the door to trigger the cellular uptake of NPs that are intended to transport drugs to their target cells in the future.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500636"},"PeriodicalIF":3.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243280","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

Decoding Structural Fingerprints to Design and Elucidate the Mechanism of Action of Prospective Cholesteryl Ester Transfer Protein Drugs. 解码结构指纹图谱，设计和阐明未来胆固醇酯转移蛋白药物的作用机制。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-10-05 DOI: 10.1002/cmdc.202500562

Sudipta Nandi, Sanjib Senapati

{"title":"Decoding Structural Fingerprints to Design and Elucidate the Mechanism of Action of Prospective Cholesteryl Ester Transfer Protein Drugs.","authors":"Sudipta Nandi, Sanjib Senapati","doi":"10.1002/cmdc.202500562","DOIUrl":"https://doi.org/10.1002/cmdc.202500562","url":null,"abstract":"Cardiovascular diseases (CVDs) have become a leading cause of deaths globally. Recent studies have shown that increasing the level of high-density lipoproteins (HDL) is one of the potential avenues to halt CVD progression. This could be achieved by modulating the neutral lipid transfer activity of cholesteryl ester transfer protein (CETP), a key target in developing effective cardioprotective drugs. This study aims to identify important structural fingerprints and functional moieties as \"good\" and \"bad\" contributors toward CETP inhibition, using machine learning (ML) and quantitative structure-activity relationship-based approaches. Results suggest unsaturated heterocyclic rings and trifluoromethyl substitutions as potential promoters and aliphatic carboxylic acid and ester moieties as the detractors in CETP inhibition. Molecular dynamics (MD) simulations of CETP in complexation with recently reported Obicetrapib with \"good\" fingerprints versus a clinically failed inhibitor, Torcetrapib shows superior inhibitory potential of the former due to stronger binding and better shape complementarity with the CETP hydrophobic tunnel. By leveraging the potentials of ML and MD simulations, this comprehensive study helps judicious pick of the right functional moieties for designing next generation CETP drugs targeting CVD.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500562"},"PeriodicalIF":3.4,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145230984","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