Bioorganic & Medicinal Chemistry最新文献_第2页

Expanding horizons: genetic code expansion technology in the study of PTM functions. 拓展视野：PTM功能研究中的遗传密码扩展技术。

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-02-01 Epub Date: 2024-12-19 DOI: 10.1016/j.bmc.2024.118049

Jingzhuo Chen, Hui Ye

引用次数: 0

Discovery of acetohydroxyacid synthase inhibitors as anti-tuberculosis lead compounds from natural products. 从天然产物中发现乙酰羟基酸合酶抑制剂作为抗结核先导化合物。

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-02-01 Epub Date: 2024-12-10 DOI: 10.1016/j.bmc.2024.118041

Yanhong Niu, Zhili Wu, Qianfang Hu, Yuchen Wu, Qihua Jiang, Xiaolan Yang

引用次数: 0

Unsymmetric hydroxylamine and hydrazine BAM15 derivatives as potent mitochondrial uncouplers. 不对称羟胺和肼BAM15衍生物作为有效的线粒体解偶联剂。

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-02-01 Epub Date: 2024-12-18 DOI: 10.1016/j.bmc.2024.118045

Joseph E Quinlan, Joseph M Salamoun, Christopher J Garcia, Stefan Hargett, Martina Beretta, Riya Shrestha, Catherine Li, Kyle L Hoehn, Webster L Santos

{"title":"Unsymmetric hydroxylamine and hydrazine BAM15 derivatives as potent mitochondrial uncouplers.","authors":"Joseph E Quinlan, Joseph M Salamoun, Christopher J Garcia, Stefan Hargett, Martina Beretta, Riya Shrestha, Catherine Li, Kyle L Hoehn, Webster L Santos","doi":"10.1016/j.bmc.2024.118045","DOIUrl":"10.1016/j.bmc.2024.118045","url":null,"abstract":"Chemical mitochondrial uncouplers are protonophoric, lipophilic small molecules that transport protons from the mitochondrial intermembrane space into the matrix independent of ATP synthase, thus uncoupling nutrient oxidation from ATP production. Our previous work identified BAM15 (IC50 0.27 μM) as a potent and efficacious mitochondrial uncoupler with potential for obesity treatment. In this paper, we investigate in vitro and in vivo properties of hydroxylamine and hydrazine BAM15 derivatives and reveal the high uncoupling nature of these compounds. Our structure-activity relationship studies revealed that the hydroxylamine BAM15 analogs are more potent than hydrazine ones. For example, the most potent of the hydrazine series was 5a with an EC50 value of 4.6 μM and 103 % activity of BAM15 while compound 4e was the best among the hydroxylamine series with EC50 value of 340 nM and 118 % BAM15 mitochondrial uncoupling activity in rat L6 myoblasts. Pharmacokinetic profiling of 5a and 4e revealed low exposure (2-220 nM) and short half-life (15-27 min) in mice.","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"118 ","pages":"118045"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

3-Halo-3-nitro-aza/thioflavanones: DNMT inhibitors with a two-site binding mode in the hDNMT3A catalytic pocket. 3-Halo-3-nitro-aza/thioflavanones：在hDNMT3A催化口袋中具有双位点结合模式的DNMT抑制剂。

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-02-01 Epub Date: 2024-11-28 DOI: 10.1016/j.bmc.2024.117988

Alexandra Serhouni, Francesco Calzaferri, Yannick Bessina, Arie van der Lee, Paola B Arimondo, Maxime Louet, Jean-Yves Winum, Marie Lopez

引用次数: 0

Exploring the antiproliferative and proapoptotic activities of new pyridopyrimidine derivatives and their analogs. 探索新型吡啶嘧啶衍生物及其类似物的抗增殖和促凋亡活性。

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-02-01 Epub Date: 2024-12-28 DOI: 10.1016/j.bmc.2024.118053

Hadeer M Ali, Mohamed A Said, Shady Allam, Hatem A Abdel-Aziz, Sahar M Abou-Seri

{"title":"Exploring the antiproliferative and proapoptotic activities of new pyridopyrimidine derivatives and their analogs.","authors":"Hadeer M Ali, Mohamed A Said, Shady Allam, Hatem A Abdel-Aziz, Sahar M Abou-Seri","doi":"10.1016/j.bmc.2024.118053","DOIUrl":"10.1016/j.bmc.2024.118053","url":null,"abstract":"This study investigates a series of newly synthesized compounds, including pyridopyrimidine derivatives (9a-g), tricyclic pyridotriazolopyrimidine analogs (18a-d), and dihydropyrimidinones (22a-i), as apoptotic inducers and inhibitors of phosphatidylinositol-3-kinase α (PI3Kα), with potential anticancer activity. An initial in vitro screening of 60 cancer cell lines identified pyridopyrimidine derivatives 9a-g as promising broad-spectrum anticancer agents, with compound 9e demonstrating the strongest inhibitory activity, particularly against T-47D breast cancer cells. Notably, the antitumor potency of compound 9e surpassed that of Pictilisib, inducing G2-M phase cell cycle arrest and initiating apoptosis through the intrinsic apoptotic pathway. Molecular docking studies further indicated that compound 9e binds to PI3Kα in a similar fashion to the co-crystallized ligand. Moreover, compound 9e exhibited favorable drug-like properties, including compliance with Lipinski's rule and Veber's rule, good solubility, acceptable TPSA, and high gastrointestinal absorption reinforcing its potential as a highly effective anticancer agent.","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"118 ","pages":"118053"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decoding the protein methylome: Identification, validation, and functional insights. 解码蛋白质甲基组：鉴定，验证和功能见解。

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-02-01 Epub Date: 2024-12-28 DOI: 10.1016/j.bmc.2024.118056

Ying Meng, Rong Huang

引用次数: 0

Quantitative profiling of PTM stoichiometry by DNA mass tags. DNA质量标签定量分析PTM化学计量学。

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-02-01 Epub Date: 2024-12-19 DOI: 10.1016/j.bmc.2024.118050

Yuanpei Li, Yuan Liu, Chu Wang

{"title":"Quantitative profiling of PTM stoichiometry by DNA mass tags.","authors":"Yuanpei Li, Yuan Liu, Chu Wang","doi":"10.1016/j.bmc.2024.118050","DOIUrl":"10.1016/j.bmc.2024.118050","url":null,"abstract":"Protein post-translational modification (PTM) serves as an important mechanism for regulating protein function. Accurate assay of PTM stoichiometry, or PTM occupancy, which refers to the proportion of proteins that contain specific modifications, is important for understanding the function of PTMs. We previously developed a novel chemoproteomic strategy \"STO-MS\" to quantify the PTM stoichiometry in complex biological samples, which employs a resolvable polymer mass tag to differentiate modified proteins and utilizes liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) techniques to measure PTM stoichiometry. However, the resolution of STO-MS is constrained by the relatively low molecular weight of the mass tag, and the incorporation of isotopic labels not only complicates the sample preparation but also restricts the measurement throughput. To address these challenges, we herein developed \"STO-MS+\", an enhanced workflow, that incorporates an optimized DNA mass tag and employs a label-free quantitative data analysis approach. We applied STO-MS+ to measure stoichiometry of three distinct PTMs, including endogenous carbonylation induced by arachidonic acid (AA), itaconation, and endogenous O-GlcNAcylation. Our work marks a notable improvement in chemoproteomic methodologies for quantifying post-translational modifications and provides a powerful analytical tool for PTM research.","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"118 ","pages":"118050"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An overview of small-molecule agents for the treatment of psoriasis. 治疗银屑病的小分子药物综述。

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-01-15 DOI: 10.1016/j.bmc.2025.118067

Zhiheng Jin, Gang Li, Dengqin He, Jiaxin Chen, Yali Zhang, Mengjie Li, Hongliang Yao

{"title":"An overview of small-molecule agents for the treatment of psoriasis.","authors":"Zhiheng Jin, Gang Li, Dengqin He, Jiaxin Chen, Yali Zhang, Mengjie Li, Hongliang Yao","doi":"10.1016/j.bmc.2025.118067","DOIUrl":"https://doi.org/10.1016/j.bmc.2025.118067","url":null,"abstract":"Psoriasis is a prevalent, chronic inflammatory disease characterized by abnormal skin plaques. To date, physical therapy, topical therapy, systemic therapy and biologic drugs are the most commonly employed strategies for treating psoriasis. Recently, many agents have advanced to clinical trials, and some anti-psoriasis drugs have been approved, including antibody drugs and small-molecule drugs. Many antibody drugs targeting cytokines and receptors, such as interleukin (IL-17 and IL-23) and tumor necrosis factor-α (TNF-α), have been approved for the treatment of psoriasis. And numerous small-molecule agents have displayed promising activities in the treatment of psoriasis. The targets of anti-psoriasis drugs encompass phosphodiesterase IV (PDE4), Janus kinase (JAK), tyrosine kinase (TYK), retinoic acid-related orphan receptors (ROR), vitamin D receptor (VDR), Interleukin (IL), Aryl hydrocarbon receptor (AhR), Interleukin-1 receptor-associated kinase 4 (IRAK), chemoattractant-like receptor 1 (ChemR23), Sphingosine-1-phosphate receptor (S1P), A3 adenosine receptor (A3AR), Heat shock protein 90 (HSP90), The Rho-associated protein kinases (ROCK), The bromodomain and extra-terminal domain (BET), FMS-like tyrosine kinase 3 (FLT3), Tumor Necrosis Factor α Converting Enzyme (TACE), Toll-like receptors (TLR), NF-κB inducing kinase (NIK), DNA topoisomerase I (Topo I), among others. Herein, this review mainly recapitulates the advancements in the structure and enzyme activity of small-molecule anti-psoriasis agents over the last ten years, and their binding modes were also explored. Hopefully, this review will facilitate the development of novel small-molecule agents as potential anti-psoriasis drugs.","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"119 ","pages":"118067"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Current strategies in design and synthesis of antifungals hybrid and chimeric diazine derivatives. 抗真菌杂合和嵌合嘧啶衍生物的设计和合成现状。

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-01-12 DOI: 10.1016/j.bmc.2025.118069

Dumitrela Diaconu, Marius Savu, Catalina Ciobanu, Violeta Mangalagiu, Ionel I Mangalagiu

引用次数: 0

Bioorthogonal chemical reporters for profiling retinoic acid-modified and retinoic acid-interacting proteins. 分析维甲酸修饰蛋白和维甲酸相互作用蛋白的生物正交化学报告。

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-01-08 DOI: 10.1016/j.bmc.2025.118065

Long Yan, Yanan Sun, Ke Ding, Tao Peng

{"title":"Bioorthogonal chemical reporters for profiling retinoic acid-modified and retinoic acid-interacting proteins.","authors":"Long Yan, Yanan Sun, Ke Ding, Tao Peng","doi":"10.1016/j.bmc.2025.118065","DOIUrl":"https://doi.org/10.1016/j.bmc.2025.118065","url":null,"abstract":"Vitamin A and its primary active derivative, all-trans retinoic acid (RA), are endogenous signaling molecules essential for numerous biological processes, including cell proliferation, differentiation, and immune modulation. Owing to its differentiation-inducing effect, RA was the first differentiating agent approved for the clinical treatment of acute myeloid leukemia. While the classical mechanisms of RA signaling involve nuclear receptors, such as retinoic acid receptors (RARs), emerging evidence suggests that RA also engages in non-covalent and covalent interactions with a broader range of proteins. However, tools for thoroughly characterizing these interactions have been lacking, and a comprehensive understanding of the landscape of RA-modified and RA-interacting proteins remains limited. Here, we report the development of two RA-based chemical reporters, RA-yne and RA-diazyne, to profile RA-modified and RA-interacting proteins, respectively, in live cells. RA-yne features a clickable alkyne group for metabolic labeling of RA-modified proteins, while RA-diazyne incorporates a photoactivatable diazirine and an alkyne handle for crosslinking and capturing RA-interacting proteins. Using quantitative proteomics, we demonstrate the high-throughput identification of these proteins, revealing that non-covalent interactions are more prevalent than covalent modifications. Our global profiling also uncovers a large number of RA-interacting proteins mainly enriched in pathways related to mitochondrial processes, ER homeostasis, and lipid metabolism. Overall, this work introduces new RA-derived chemical reporters, expands the resource for studying RA biology, and enhances our understanding of RA-associated pathways in health and disease.","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"119 ","pages":"118065"},"PeriodicalIF":3.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0