Molecules最新文献_第9页

Exploration of the Solubility Hyperspace of Selected Active Pharmaceutical Ingredients in Choline- and Betaine-Based Deep Eutectic Solvents: Machine Learning Modeling and Experimental Validation. 精选活性药物成分在胆碱和甜菜碱基深共晶溶剂中的溶解度超空间探索：机器学习建模与实验验证。

IF 4.2 2区化学

Molecules Pub Date : 2024-10-16 DOI: 10.3390/molecules29204894

Piotr Cysewski, Tomasz Jeliński, Maciej Przybyłek

{"title":"Exploration of the Solubility Hyperspace of Selected Active Pharmaceutical Ingredients in Choline- and Betaine-Based Deep Eutectic Solvents: Machine Learning Modeling and Experimental Validation.","authors":"Piotr Cysewski, Tomasz Jeliński, Maciej Przybyłek","doi":"10.3390/molecules29204894","DOIUrl":"https://doi.org/10.3390/molecules29204894","url":null,"abstract":"Deep eutectic solvents (DESs) are popular green media used for various industrial, pharmaceutical, and biomedical applications. However, the possible compositions of eutectic systems are so numerous that it is impossible to study all of them experimentally. To remedy this limitation, the solubility landscape of selected active pharmaceutical ingredients (APIs) in choline chloride- and betaine-based deep eutectic solvents was explored using theoretical models based on machine learning. The available solubility data for the selected APIs, comprising a total of 8014 data points, were collected for the available neat solvents, binary solvent mixtures, and DESs. This set was augmented with new measurements for the popular sulfa drugs in dry DESs. The descriptors used in the machine learning protocol were obtained from the σ-profiles of the considered molecules computed within the COSMO-RS framework. A combination of six sets of descriptors and 36 regressors were tested. Taking into account both accuracy and generalization, it was concluded that the best regressor is nuSVR regressor-based predictive models trained using the relative intermolecular interactions and a twelve-step averaged simplification of the relative σ-profiles.","PeriodicalId":19041,"journal":{"name":"Molecules","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Photoinduced Transformations with Diverse Maleimide Scaffolds. 多种马来酰亚胺支架的光诱导转化。

IF 4.2 2区化学

Molecules Pub Date : 2024-10-16 DOI: 10.3390/molecules29204895

Jayachandran Parthiban, Dipti Garg, Jayaraman Sivaguru

引用次数: 0

Synthesis, Urease Inhibition, Molecular Docking, and Optical Analysis of a Symmetrical Schiff Base and Its Selected Metal Complexes. 对称席夫碱及其选定金属配合物的合成、尿素酶抑制、分子对接和光学分析。

IF 4.2 2区化学

Molecules Pub Date : 2024-10-16 DOI: 10.3390/molecules29204899

Samuel Bonne, Muhammad Saleem, Muhammad Hanif, Joseph Najjar, Salahuddin Khan, Muhammad Zeeshan, Tehreem Tahir, Anser Ali, Changrui Lu, Ting Chen

{"title":"Synthesis, Urease Inhibition, Molecular Docking, and Optical Analysis of a Symmetrical Schiff Base and Its Selected Metal Complexes.","authors":"Samuel Bonne, Muhammad Saleem, Muhammad Hanif, Joseph Najjar, Salahuddin Khan, Muhammad Zeeshan, Tehreem Tahir, Anser Ali, Changrui Lu, Ting Chen","doi":"10.3390/molecules29204899","DOIUrl":"10.3390/molecules29204899","url":null,"abstract":"Designing and developing small organic molecules for use as urease inhibitors is challenging due to the need for ecosystem sustainability and the requirement to prevent health risks related to the human stomach and urinary tract. Moreover, imaging analysis is widely utilized for tracking infections in intracellular and in vivo systems, which requires drug molecules with emissive potential, specifically in the low-energy region. This study comprises the synthesis of a Schiff base ligand and its selected transition metals to evaluate their UV/fluorescence properties, inhibitory activity against urease, and molecular docking. Screening of the symmetrical cage-like ligand and its metal complexes with various eco-friendly transition metals revealed significant urease inhibition potential. The IC50 value of the ligand for urease inhibition was 21.80 ± 1.88 µM, comparable to that of thiourea. Notably, upon coordination with transition metals, the ligand-nickel and ligand-copper complexes exhibited even greater potency than the reference compound, with IC50 values of 11.8 ± 1.14 and 9.31 ± 1.31 µM, respectively. The ligand-cobalt complex exhibited an enzyme inhibitory potential comparable with thiourea, while the zinc and iron complexes demonstrated the least activity, which might be due to weaker interactions with the investigated protein. Meanwhile, all the metal complexes demonstrated a pronounced optical response, which could be utilized for fluorescence-guided targeted drug delivery applications in the future. Molecular docking analysis and IC50 values from in vitro urease inhibition screening showed a trend of increasing activity from compounds 7d to 7c to 7b. Enzyme kinetics studies using the Lineweaver-Burk plot indicated mixed-type inhibition against 7c and non-competitive inhibition against 7d.","PeriodicalId":19041,"journal":{"name":"Molecules","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Enhancement and Compatibilization of Waste-Sourced Biocomposites Through Elastomer Blending and Matrix Grafting Modification. 通过弹性体混合和基质接枝改性提高废物来源生物复合材料的性能和相容性。

IF 4.2 2区化学

Molecules Pub Date : 2024-10-16 DOI: 10.3390/molecules29204905

Shunmin Yi, Wanyu Liu, Shihua Xu, Ruijia Hu, Qing Li, Meijia Wu, Qingwen Wang, Zhimin Huang

{"title":"Enhancement and Compatibilization of Waste-Sourced Biocomposites Through Elastomer Blending and Matrix Grafting Modification.","authors":"Shunmin Yi, Wanyu Liu, Shihua Xu, Ruijia Hu, Qing Li, Meijia Wu, Qingwen Wang, Zhimin Huang","doi":"10.3390/molecules29204905","DOIUrl":"https://doi.org/10.3390/molecules29204905","url":null,"abstract":"A novel elastomer-modified multicomponent, multiphase waste-sourced biocomposites, was prepared for converting waste biomass and plastic into value-added products. The effects of blending elastomer-olefin block copolymer (OBC) and maleic anhydride (MAH), and divinylbenzene (DVB) co-grafting of recycled polypropylene (rPP) matrix on the adhesion interface, structure, and properties of high wood flour-filled (60 wt.%) composites were thoroughly investigated. The results indicated that DVB introduced branched structures into the polymer matrix molecular chain and increased the MAH grafting rate. Co-grafting rPP/OBC blends enhanced the interfacial adhesion among rPP, OBC, and wood flour. Additionally, MAH-grafted OBC was prone to encapsulating rigid wood flour, thereby forming an embedded structure. Notably, the tensile modulus and impact strength of the final three-component composites increased by 60% and 125%, respectively, compared with the unmodified composites. Additionally, dynamic mechanical analysis revealed that DVB-induced branching promoted the formation of microvoids in the OBC shell layer surrounding the wood, which in turn induced significant plastic deformation in the polymer matrix. This work offers a facile and efficient method for preparing high-toughness, high-stiffness, and low-cost waste PP-based composites for automotive interiors, and indoor and outdoor decoration.","PeriodicalId":19041,"journal":{"name":"Molecules","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Unveiling New Horizons: Advancing Technologies in Cosmeceuticals for Anti-Aging Solutions. 揭开新地平线：用于抗衰老解决方案的药妆先进技术。

IF 4.2 2区化学

Molecules Pub Date : 2024-10-15 DOI: 10.3390/molecules29204890

Patrícia Lius Melo Alves, Vitor Nieri, Fernanda de Campos Moreli, Ederson Constantino, Jocimar de Souza, Yoko Oshima-Franco, Denise Grotto

{"title":"Unveiling New Horizons: Advancing Technologies in Cosmeceuticals for Anti-Aging Solutions.","authors":"Patrícia Lius Melo Alves, Vitor Nieri, Fernanda de Campos Moreli, Ederson Constantino, Jocimar de Souza, Yoko Oshima-Franco, Denise Grotto","doi":"10.3390/molecules29204890","DOIUrl":"https://doi.org/10.3390/molecules29204890","url":null,"abstract":"In the last years, the landscape of anti-aging cosmetics has been marked by significant advances in cosmeceutical delivery systems. This study aimed to conduct a systematic review of these technological innovations, with a focus on anti-aging effects, from 2018 to 2023. The methodology included a thorough search on PubMed and through gray literature, applying rigorous exclusion criteria. The descriptors were selected based on the Medical Subject Headings (MeSH). A total of 265 articles were found. Exclusion criteria were applied, and 90 of them were selected for full reading. After reading the full 90 articles, 52 were excluded, leaving 38 articles for final evaluation composing this review. The key findings highlighted a clear prevalence of studies exploring nanotechnology, including nanoparticles, niosomes, and liposomes. Most of the formulations analyzed in this review emphasize antioxidant activities, which play a crucial role in preventing premature aging caused by free radicals. The reviewed studies revealed specific activities, such as the reduction in melanin synthesis, the inhibition of enzymes involved in the skin aging process, and the prevention of morphological changes typical of aging.","PeriodicalId":19041,"journal":{"name":"Molecules","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Enhanced Electrochemiluminescence of Luminol and-Dissolved Oxygen by Nanochannel-Confined Au Nanomaterials for Sensitive Immunoassay of Carcinoembryonic Antigen. 纳米通道封闭金纳米材料增强鲁米诺和溶解氧的电化学发光，用于癌胚抗原的灵敏免疫测定

IF 4.2 2区化学

Molecules Pub Date : 2024-10-15 DOI: 10.3390/molecules29204880

Weibin Li, Ruliang Yu, Fengna Xi

{"title":"Enhanced Electrochemiluminescence of Luminol and-Dissolved Oxygen by Nanochannel-Confined Au Nanomaterials for Sensitive Immunoassay of Carcinoembryonic Antigen.","authors":"Weibin Li, Ruliang Yu, Fengna Xi","doi":"10.3390/molecules29204880","DOIUrl":"https://doi.org/10.3390/molecules29204880","url":null,"abstract":"Simple development of an electrochemiluminescence (ECL) immunosensor for convenient detection of tumor biomarker is of great significance for early cancer diagnosis, treatment evaluation, and improving patient survival rates and quality of life. In this work, an immunosensor is demonstrated based on an enhanced ECL signal boosted by nanochannel-confined Au nanomaterial, which enables sensitive detection of the tumor biomarker-carcinoembryonic antigen (CEA). Vertically-ordered mesoporous silica film (VMSF) with a nanochannel array and amine groups was rapidly grown on a simple and low-cost indium tin oxide (ITO) electrode using the electrochemically assisted self-assembly (EASA) method. Au nanomaterials were confined in situ on the VMSF through electrodeposition, which catalyzed both the conversion of dissolved oxygen (O2) to reactive oxygen species (ROS) and the oxidation of a luminol emitter and improved the electrode active surface. The ECL signal was enhanced fivefold after Au nanomaterial deposition. The recognitive interface was fabricated by covalent immobilization of the CEA antibody on the outer surface of the VMSF, followed with the blocking of non-specific binding sites. In the presence of CEA, the formed immunocomplex reduced the diffusion of the luminol emitter, resulting in the reduction of the ECL signal. Based on this mechanism, the constructed immunosensor was able to provide sensitive detection of CEA ranging from 1 pg·mL-1 to 100 ng·mL-1 with a low limit of detection (LOD, 0.37 pg·mL-1, S/N = 3). The developed immunosensor exhibited high selectivity and good stability. ECL determination of CEA in fetal bovine serum was achieved.","PeriodicalId":19041,"journal":{"name":"Molecules","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Multi-Wavelength Excitable Multicolor Upconversion and Ratiometric Luminescence Thermometry of Yb³⁺/Er³⁺ Co-Doped NaYGeO₄ Microcrystals. Yb3+/Er3+ 共掺 NaYGeO4 微晶的多波长可激发多色上转换和比率发光测温。

IF 4.2 2区化学

Molecules Pub Date : 2024-10-15 DOI: 10.3390/molecules29204887

Hui Zeng, Yangbo Wang, Xiaoyi Zhang, Xiangbing Bu, Zongyi Liu, Huaiyong Li

{"title":"Multi-Wavelength Excitable Multicolor Upconversion and Ratiometric Luminescence Thermometry of Yb3+/Er3+ Co-Doped NaYGeO4 Microcrystals.","authors":"Hui Zeng, Yangbo Wang, Xiaoyi Zhang, Xiangbing Bu, Zongyi Liu, Huaiyong Li","doi":"10.3390/molecules29204887","DOIUrl":"https://doi.org/10.3390/molecules29204887","url":null,"abstract":"Excitation wavelength controllable lanthanide upconversion allows for real-time manipulation of luminescent color in a composition-fixed material, which has been proven to be conducive to a variety of applications, such as optical anti-counterfeiting and information security. However, current available materials highly rely on the elaborate core-shell structure in order to ensure efficient excitation-dependent energy transfer routes. Herein, multicolor upconversion luminescence in response to both near-infrared I and near-infrared II (NIR-I and NIR-II) excitations is realized in a novel but simple NaYGeO4:Yb3+/Er3+ phosphor. The remarkably enhanced red emission ratio under 1532 nm excitation, compared with that under 980 nm excitation, could be attributed to the Yb3+-mediated cross-relaxation energy transfers. Moreover, multi-wavelength excitable temperature-dependent (295-823 K) upconversion luminescence realizes a ratiometric thermometry relying on the thermally coupled levels (TCLs) of Er3+. Detailed investigations demonstrate that changing excitation wavelength makes little difference for the performances of TCL-based ratiometric thermometry of NaYGeO4:Yb3+/Er3+. These findings gain more insights to manipulate cross-relaxations for excitation controllable upconversion in single activator doped materials and benefit the cognition of the effect of excitation wavelength on ratiometric luminescence thermometry.","PeriodicalId":19041,"journal":{"name":"Molecules","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Recent Progress in Terrestrial Biota Derived Antibacterial Agents for Medical Applications. 陆地生物群衍生抗菌剂在医疗应用方面的最新进展。

IF 4.2 2区化学

Molecules Pub Date : 2024-10-15 DOI: 10.3390/molecules29204889

Todorka G Vladkova, Younes Smani, Boris L Martinov, Dilyana N Gospodinova

{"title":"Recent Progress in Terrestrial Biota Derived Antibacterial Agents for Medical Applications.","authors":"Todorka G Vladkova, Younes Smani, Boris L Martinov, Dilyana N Gospodinova","doi":"10.3390/molecules29204889","DOIUrl":"https://doi.org/10.3390/molecules29204889","url":null,"abstract":"Conventional antibiotic and multidrug treatments are becoming less and less effective and the discovery of new effective and safe antibacterial agents is becoming a global priority. Returning to a natural antibacterial product is a relatively new current trend. Terrestrial biota is a rich source of biologically active substances whose antibacterial potential has not been fully utilized. The aim of this review is to present the current state-of-the-art terrestrial biota-derived antibacterial agents inspired by natural treatments. It summarizes the most important sources and newly identified or modified antibacterial agents and treatments from the last five years. It focuses on the significance of plant- animal- and bacteria-derived biologically active agents as powerful alternatives to antibiotics, as well as the advantages of utilizing natural antibacterial molecules alone or in combination with antibiotics. The main conclusion is that terrestrial biota-derived antibacterial products and substances open a variety of new ways for modern improved therapeutic strategies. New terrestrial sources of known antibacterial agents and new antibacterial agents from terrestrial biota were discovered during the last 5 years, which are under investigation together with some long-ago known but now experiencing their renaissance for the development of new medical treatments. The use of natural antibacterial peptides as well as combinational therapy by commercial antibiotics and natural products is outlined as the most promising method for treating bacterial infections. In vivo testing and clinical trials are necessary to reach clinical application.","PeriodicalId":19041,"journal":{"name":"Molecules","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Serendipitous Conversion of an Acetylamino Dideoxy-Octonic Acid Derivate into a Functionalized Carbohydrate-Pyrazole Conjugate and Investigation of the Method´s General Applicability. 偶然将乙酰氨基二脱氧辛酸衍生物转化为功能化碳水化合物-吡唑共轭物并研究该方法的普遍适用性。

IF 4.2 2区化学

Molecules Pub Date : 2024-10-15 DOI: 10.3390/molecules29204885

Jelena K Berl, Christian Czaschke, Ann-Kathrin Pramor, Christian B W Stark, Joachim Thiem

{"title":"Serendipitous Conversion of an Acetylamino Dideoxy-Octonic Acid Derivate into a Functionalized Carbohydrate-Pyrazole Conjugate and Investigation of the Method´s General Applicability.","authors":"Jelena K Berl, Christian Czaschke, Ann-Kathrin Pramor, Christian B W Stark, Joachim Thiem","doi":"10.3390/molecules29204885","DOIUrl":"https://doi.org/10.3390/molecules29204885","url":null,"abstract":"By treatment of the peracetylated methylester of 4-acetylamino-2,4-dideoxy-d-glycero-d-galacto-octonic acid (ADOA-PAE) with nitrosyl tetrafluoroborate, a serendipitous formation of a highly functionalized carbohydrate-pyrazole conjugate was observed in 95% yield. This observation is remarkable, as it involves a five-step one-pot synthesis that proceeds via an 1,3-acyl shift and a 1,5-electrocyclization, which usually requires thermal conditions; however, the reaction occurred at a temperature of 0 °C. Additionally, the excellent yield of the carbohydrate-decorated pyrazole and the regiospecificity of the cyclization are of particular interest, as regioselectivity is always a challenge in pyrazole synthesis. Subsequently, this novel access to pyrazoles starting from N-acetyl-allyl amides via nitrosation and electrocyclization was investigated. In addition, mechanistic studies for the formation of substituted pyrazoles of type were carried out.","PeriodicalId":19041,"journal":{"name":"Molecules","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11509885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Identification of Novel PPARγ Partial Agonists Based on Virtual Screening Strategy: In Silico and In Vitro Experimental Validation. 基于虚拟筛选策略的新型 PPARγ 部分激动剂的鉴定：硅学和体外实验验证。

IF 4.2 2区化学

Molecules Pub Date : 2024-10-15 DOI: 10.3390/molecules29204881

Yu-E Lian, Mei Wang, Lei Ma, Wei Yi, Siyan Liao, Hui Gao, Zhi Zhou

{"title":"Identification of Novel PPARγ Partial Agonists Based on Virtual Screening Strategy: In Silico and In Vitro Experimental Validation.","authors":"Yu-E Lian, Mei Wang, Lei Ma, Wei Yi, Siyan Liao, Hui Gao, Zhi Zhou","doi":"10.3390/molecules29204881","DOIUrl":"10.3390/molecules29204881","url":null,"abstract":"Thiazolidinediones (TZDs) including rosiglitazone and pioglitazone function as peroxisome proliferator-activated receptor gamma (PPARγ) full agonists, which have been known as a class to be among the most effective drugs for the treatment of type 2 diabetes mellitus (T2DM). However, side effects of TZDs such as fluid retention and weight gain are associated with their full agonistic activities toward PPARγ induced by the AF-2 helix-involved \"locked\" mechanism. Thereby, this study aimed to obtain novel PPARγ partial agonists without direct interaction with the AF-2 helix. Through performing virtual screening of the Targetmol L6000 Natural Product Library and utilizing molecular dynamics (MD) simulation, as well as molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis, four compounds including tubuloside b, podophyllotoxone, endomorphin 1 and paliperidone were identified as potential PPARγ partial agonists. An in vitro TR-FRET competitive binding assay showed podophyllotoxone displayed the optimal binding affinity toward PPARγ among the screened compounds, exhibiting IC50 and ki values of 27.43 µM and 9.86 µM, respectively. Further cell-based transcription assays were conducted and demonstrated podophyllotoxone's weak agonistic activity against PPARγ compared to that of the PPARγ full agonist rosiglitazone. These results collectively demonstrated that podophyllotoxone could serve as a PPARγ partial agonist and might provide a novel candidate for the treatment of various diseases such as T2DM.","PeriodicalId":19041,"journal":{"name":"Molecules","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11509912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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