Bioorganic Chemistry最新文献

{"title":"Functionalized Thiadiazole: Synthesis, insecticidal activity, molecular docking and DFT studies of some new 5-substituted 1,2,4-Thiadiazoles based on Norfloxacin","authors":"Ahmed M. El-Saghier ,&nbsp;Laila Abosella ,&nbsp;Aly Abdou ,&nbsp;Magda H. Abdellattif ,&nbsp;Mohamed A. Gad","doi":"10.1016/j.bioorg.2025.108510","DOIUrl":"10.1016/j.bioorg.2025.108510","url":null,"abstract":"<div><div>Through plant protection, we hope to contribute to the growth of cotton production—the most significant non-food agricultural commodity. The use of safe substitutes for pesticides has become essential because of a number of grave problems related to their use. Consequently, families of novel environmentally benign Norfloxacin series with insecticidal efficacy based on 5-Substituted 1,2,4-thiadiazoles were identified. The Target synthesized compounds were confirmed by elemental and modern spectroscopic analyses (such as IR, UV, ¹H NMR and ¹³C NMR). The toxicological activity of this compounds were checked towards nymphs and adults of <em>Aphis gossypii</em> which the most affected compound <strong>7</strong> had an LC₅₀ of 0.907 mg/L, while the LC₅₀ of commercial thiacloprid was 0.255 mg/L. Due to the presence of carboxalic acid and fluorophenyl groups in their chemical composition, component <strong>7</strong> may be especially effective. Density Functional Theory (DFT) analysis of the synthesized compounds using the B3LYP hybrid functional and the 6-311G(d,p) basis set provided valuable insights into their electronic properties and chemical reactivity. Frontier Molecular Orbital (FMO) analysis revealed that compound <strong>7</strong>, with the smallest HOMO-LUMO gap (ΔE = 2.94 eV), exhibited the highest reactivity, suggesting its potential for significant biological interactions. Moreover, molecular docking studies against the 4EY4 hydrolase enzyme indicated strong binding affinities for compounds <strong>3, 5, 7</strong> and <strong>8</strong> with docking scores surpassing the standard Thiacloprid, confirming their enhanced bioactivity. These results, when correlated with quantum chemical parameters and biological assays, highlight the promising therapeutic potential of the new compounds, especially compound <strong>7</strong>.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108510"},"PeriodicalIF":4.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of anti-MRSA carpatamides' congeners by heterologous expression along with their mechanism investigation targeting FabI and biofilm formation","authors":"Shumei Shen ,&nbsp;Hongtao Duan ,&nbsp;Yunchang Xie ,&nbsp;Kai Liu ,&nbsp;Lirong Tu ,&nbsp;Bo Yang ,&nbsp;Yanmin Wang ,&nbsp;Chunhui Song ,&nbsp;Yuhui Sun ,&nbsp;Minghe Luo","doi":"10.1016/j.bioorg.2025.108518","DOIUrl":"10.1016/j.bioorg.2025.108518","url":null,"abstract":"<div><div>Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) remains a significant clinical challenge, necessitating the discovery of novel anti-MRSA agents. Previous bioinformatic analysis identified a candidate biosynthetic gene cluster (BGC) of <em>ctd</em> for carpatamides in <em>Streptomyces parvus</em> 1268. Through heterologous expression of <em>ctd</em> and subsequent fermentation and isolation, we have identified five novel carpatamide derivatives of carpatamides N − R (<strong>1</strong>–<strong>5</strong>), and a known compound of daryamide A (<strong>6</strong>). The structures and absolute configurations of compounds <strong>1</strong>–<strong>6</strong> were determined by ESI-HRMS, NMR, and ECD calculations. Compound <strong>1</strong> exhibited significant antitumor activity against non-small cell lung cancer cell line A549 with an IC₅₀ value of 7.43 μM. Meanwhile, the antibacterial bioactivity results showed that carpatamides N − O (<strong>1</strong>–<strong>2</strong>) displayed excellent antibacterial bioassay against Gram-positive bacteria, including MRSA with MIC values of 0.5–2.0 μg/mL, outperforming vancomycin. Further mechanism investigation through molecular dynamics (MD) simulations and biofilm-related experiments suggests that compounds <strong>1</strong> and <strong>2</strong> may exert their anti-MRSA activity by inhibiting the function of NADPH-dependent enoyl-acyl carrier protein reductase (FabI) and the formation of biofilms of MRSA.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108518"},"PeriodicalIF":4.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating untargeted metabolomics and computational docking for biomarker evaluation: A case study on marine algae-derived ligands","authors":"Hamada A.A. Noreldeen ,&nbsp;Abdel-Rahman M. Hamed ,&nbsp;Mohamed El-Shazly ,&nbsp;Abeer A. El-Saharty ,&nbsp;Osman A. Farghaly ,&nbsp;Shouxiong Huang","doi":"10.1016/j.bioorg.2025.108539","DOIUrl":"10.1016/j.bioorg.2025.108539","url":null,"abstract":"<div><div>In the post-genomic era, liquid chromatography-mass spectrometry (LC-MS) has emerged as a powerful tool for profiling metabolic profiles in marine macroalgae, which are known for their chemical diversity and pharmacological potential. This study integrates untargeted metabolomics and computational chemistry to accelerate the discovery of therapeutic agents from two red algae (<em>Jania rubens</em> and <em>Scinaia fascicularis</em>) and two brown algae (<em>Hydroclathrus clathratus</em> and <em>Sargassum cinereum</em>). LC-MS-based analysis revealed genotypic variations influencing compound structures, functional groups, and physicochemical properties, which correlated with biological activity scores. Ligand-based virtual screening identified lead compounds with high therapeutic potential, while structure-based virtual screening highlighted stigmasta-5,24(28)-dien-3-ol (3α,24Z) (SM) as the top-ranked ligand, exhibiting a binding affinity of −11.40 kcal/mol. Docking optimization at exhaustiveness levels of 8, 16, and 32 demonstrated that level 8 achieved the best balance of accuracy and computational efficiency, completing in 49.74 s. Post-docking evaluation, including statistical analysis, validated the results, with ubiquinol-cytochrome-c reductase protein showing moderate-to-high activity scores for the selected compounds. These findings underscore the potential of marine algae-derived compounds as therapeutic agents, though further in vitro and in vivo studies are needed to confirm their bioactivity. This work highlights the importance of precise extraction and identification of bioactive compounds for advancing marine natural product research.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108539"},"PeriodicalIF":4.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fingerprint of ubiquitin coupled enzyme UBC13 in health and disease","authors":"Ru-Yi Chen ,&nbsp;Yan-Jun Liu ,&nbsp;Ran Wang,&nbsp;Jing Yu,&nbsp;Jin-Jin Shi,&nbsp;Guan-Jun Yang,&nbsp;Jiong Chen","doi":"10.1016/j.bioorg.2025.108524","DOIUrl":"10.1016/j.bioorg.2025.108524","url":null,"abstract":"<div><div>Ubiquitination is one of the most well-known post-translational modifications in eukaryotes. UBC13 is an E2 ubiquitin coupling enzyme, which interacts with different E3 ligases and exerts ubiquitination activity to assemble and synthesize lysine-63-linked (Lys63) ubiquitin strands, thus playing an important role in cell homeostasis, various diseases caused by inflammation, and the occurrence and development of cancer. In this paper, we review the structure and function of UBC13, summarize the diverse pathways it mediates, and discuss its involvement in bacterial and non-bacterial inflammatory diseases. Additionally, we explore UBC13's role in physiological damage repair mechanisms, cancer development, DNA damage repair, immune cell maturation, and function. Furthermore, We also elucidate the progress of the discovery of small molecule inhibitors targeting UBC13 and summarize their structure, which suggests that targeting UBC13 may be a potential disease treatment strategy.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108524"},"PeriodicalIF":4.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gardenin A alleviates alcohol-induced oxidative stress and inflammation in HepG2 and Caco2 cells via AMPK/Nrf2 pathway","authors":"Prashsti Chadha ,&nbsp;Hiral Aghara ,&nbsp;Delna Johnson ,&nbsp;Dhrubjyoti Sharma ,&nbsp;Mitalben Odedara ,&nbsp;Manali Patel ,&nbsp;Hemant Kumar ,&nbsp;Vijay Thiruvenkatam ,&nbsp;Palash Mandal","doi":"10.1016/j.bioorg.2025.108543","DOIUrl":"10.1016/j.bioorg.2025.108543","url":null,"abstract":"<div><div>Chronic alcohol consumption triggers immune responses that lead to cell damage, contributing to alcohol-associated liver disease (ALD). Despite its prevalence, no FDA-approved treatment for ALD currently exists. This study explores the cytoprotective effects of Gardenin A (GarA), a polymethoxylated flavone, for protection against alcohol-induced oxidative stress and inflammation in HepG2 and Caco2 cell lines. GarA was isolated, characterized and, tested <em>in-vitro</em>, showing maximum cell viability at 10 μg/ml using MTT assays. Further, lipid accumulation assay, reactive oxygen species (ROS) estimation and nuclear morphology visualization was carried out using different staining techniques. RT-qPCR was employed to examine the expression of various pro- and anti-inflammatory cytokines, along with Cytochrome P4502E1 (CYP2E1) and Sterol regulatory element binding protein-2 (SREBP2) and tight junction genes crucial for gut barrier integrity. Moreover, ELISA was carried out for key protein targets such as AMPK (phosphorylated and total), TNFα, C5aR1, HO-1 and Nrf2. GarA caused a marked decrease in lipid droplets, ROS levels, and expression of pro-inflammatory cytokines. It showed anti-inflammatory and anti-oxidant activity and helped maintain the gut barrier and nuclear integrity. <em>In-silico</em> studies showed the conserved amino acid interaction and affinity of GarA with C5aR1, and TNFα, compared to the interactions with known inhibitors/activators, further corroborating the results. This study is the first to explore the effects of GarA on ALD, underscoring its potential as an anti-inflammatory and anti-oxidant agent targeting the AMPK/Nrf2 signaling pathway, suggesting its future as a promising therapeutic candidate for mitigating alcohol-induced liver and gut damage.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108543"},"PeriodicalIF":4.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and synthesis of novel 2-S-alkylated Quinazolinones as dual BRAFV600E and EGFR inhibitors in melanoma: Mechanistic insights from apoptosis and cell cycle modulation","authors":"Hamed W. El-Shafey ,&nbsp;Mohammad M. Al-Sanea ,&nbsp;Mohamed R. Elnagar ,&nbsp;Abdallah M. Gendy ,&nbsp;Marwa I. Serag ,&nbsp;Aya M. Almatary ,&nbsp;Mohamed A. Khalaf ,&nbsp;Maha-Hamadien Abdulla ,&nbsp;Noura S. Alhassan ,&nbsp;Mansoor-Ali Vaali Mohammed ,&nbsp;Wagdy M. Eldehna ,&nbsp;Abdelrahman Hamdi","doi":"10.1016/j.bioorg.2025.108526","DOIUrl":"10.1016/j.bioorg.2025.108526","url":null,"abstract":"<div><div>Melanoma, an aggressive and highly metastatic form of skin cancer, remains challenging to treat due to its resistance to conventional therapies and frequent mutations in the BRAF signaling pathway. In this study, we report the design and synthesis of a novel series of thirteen quinazolinone derivatives, featuring a phenyl thiazole moiety linked via a triazole acetamide spacer. These compounds were developed as potential dual inhibitors of BRAF^V600E and EGFR, which should offer a promising therapeutic strategy for melanoma treatment. The antiproliferative activity of these compounds was evaluated against the NCI-60 cell line panel, with six compounds advancing to a five-dose screening. Three compounds, <strong>7</strong><strong>k, 7</strong><strong>l, and 7</strong><strong>m</strong>, exhibited broad-spectrum anticancer activity, with mean growth inhibition (GI%) exceeding 100 %. Compound 7<strong>l</strong> demonstrated exceptional efficacy against melanoma subpanels (GI% = 152 %) and potent dual kinase inhibition, with IC₅₀ values of 0.048 μM against B-RAF^V600E and 0.037 μM against EGFR. In vitro studies of compound <strong>7</strong><strong>l</strong> revealed significant cytotoxicity against MALME-3 M (IC₅₀ = 3.16 μM) and LOX-IMVI (IC₅₀ = 2.50 μM) melanoma cell lines, with minimal toxicity towards normal Vero cells. Cell cycle analysis showed G1-phase arrest and disrupted DNA synthesis in melanoma cells, while apoptosis assays demonstrated a dramatic increase in early apoptotic cells from 7.28 % to 40.69 %. Compound <strong>7</strong><strong>l</strong> modulated key apoptotic markers, increasing the BAX/Bcl-2 ratio by 14.42-fold and elevating caspase 3 and 9 levels, indicating its potential to overcome drug resistance and enhance therapeutic efficacy in melanoma treatment.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108526"},"PeriodicalIF":4.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and synthesis of novel Hydroxamate and non-Hydroxamate HDAC inhibitors based on Chromone and Quinazolone scaffolds","authors":"Rosaline Ashraf ,&nbsp;Mai Adel ,&nbsp;Rabah A.T. Serya ,&nbsp;Esraa Ibrahim ,&nbsp;Hesham Haffez ,&nbsp;Sameh Soror ,&nbsp;Khaled A.M. Abouzid","doi":"10.1016/j.bioorg.2025.108514","DOIUrl":"10.1016/j.bioorg.2025.108514","url":null,"abstract":"<div><div>The development of selective histone deacetylase (HDAC) inhibitors represents an encouraging approach for cancer therapy. In this study, we report design, synthesis, and biological evaluation of hydroxamate, amidoxime, and carboxylic acid-based derivatives as novel HDAC inhibitors. The synthesized compounds were assessed for their inhibitory activity against multiple HDAC isoforms, particularly HDAC6, 7, and 8. Compounds <strong>13, 16, 20,</strong> and <strong>26</strong> exhibited potent and selective inhibition of HDAC6. Compound <strong>26</strong> exhibited the most potent inhibitory activity against HDAC6, with an IC₅₀ value of 70 nM. Additionally, compounds <strong>17</strong> and <strong>23</strong> demonstrated significant broad-spectrum antiproliferative activity across various cancer cell lines compared to other tested derivatives. Furthermore, compounds <strong>17</strong> and <strong>23</strong> showed promising total pan-HDAC inhibitory activity. Subsequent biological studies revealed that compounds <strong>13, 16, 17, 20, 23,</strong> and <strong>26</strong> induced a combination of early and late apoptosis along with necrosis. <em>In silico</em> studies, including molecular docking and ADME predictions, were also conducted. Collectively, these findings highlight the potential of these compounds as promising candidates for the development of a novel class of selective HDAC6 inhibitors in the future.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108514"},"PeriodicalIF":4.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triketone-acylphloroglucinol-monoterpenoid hybrids from Callistemon viminalis, a new structural template of anti-cardiac hypertrophy","authors":"Qing-Hong Meng ,&nbsp;Yan-Jie Huang ,&nbsp;Long-Gao Xiao ,&nbsp;Xue-Yu Yang ,&nbsp;Xiao-Zhi He ,&nbsp;Rui-Qi Liu ,&nbsp;Shan-Shan Ling ,&nbsp;Huan Yan ,&nbsp;Xin Fang ,&nbsp;Hui Liu ,&nbsp;Hai-Yang Liu","doi":"10.1016/j.bioorg.2025.108542","DOIUrl":"10.1016/j.bioorg.2025.108542","url":null,"abstract":"<div><div>Seven new β-triketone-acylphloroglucinol-monoterpenoid hybrids, namely callistevimones A-G (<strong>1</strong>–<strong>7</strong>), were isolated from <em>Callistemon viminalis</em> fruits. Their structures and absolute stereochemistry were accomplished through a comprehensive analytical method involving mass spectrometry, NMR, ECD calculation, QM-NMR calculation, and single-crystal X-ray crystallography. Compounds <strong>1</strong> and <strong>2</strong> are first examples of β-triketone-acylphloroglucinol-phellandrene with an enlarged-ring. Subsequently, the effects of these compounds on cardiac hypertrophy and heart failure were investigated in vitro for the first time. The results showed that compounds <strong>2</strong>, and <strong>5</strong>–<strong>7</strong> significantly reversed isoinduced hypertrophic phenotype and the reduction of mitochondrial membrane potential in AC16 cells. Furthermore, these compounds significantly increased the mRNA expression and protein expression of MPC1 (mitochondrial pyruvate carrier 1), an emerging mediator of heart failure. Concurrently, these compounds increased glucose consumption, glycolysis, and the transportation of pyruvate into mitochondria in AC16 cells using ¹³C₆-labeled glucose and ¹³C₃-labeled pyruvate tracing. In conclusion, compounds <strong>2</strong> and <strong>5</strong>–<strong>7</strong> are potential for reversing isoinduced cardiac hypertrophy and energy metabolism disorders by increasing MPC1 activity, thus having potential therapeutic implications for the treatment of cardiac hypertrophy and heart failure.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108542"},"PeriodicalIF":4.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel one−/two-photon excited β-carboline/quinolinium photosensitizers for hypoxia-resistant tumor photodynamic therapy through apoptosis and necrosis","authors":"Dongliang Ji ,&nbsp;Jian Chen ,&nbsp;Yifan Ma ,&nbsp;Yangyang Jiang ,&nbsp;Ke Xu ,&nbsp;Zifei Yuan ,&nbsp;Yong Ling ,&nbsp;Tao Yang ,&nbsp;Yanan Zhang","doi":"10.1016/j.bioorg.2025.108538","DOIUrl":"10.1016/j.bioorg.2025.108538","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) represents an innovative modality that employs photosensitizer for the treatment of tumors, dermatological conditions, and vascular disorders. Herein, a series of novel photosensitizers <strong>2a-e</strong> were designed and synthesized by incorporating quinolinium into the β-carboline. In particular, photosensitizer <strong>2d</strong> generated a large amount of type-I/-II active oxygen species, including ¹O₂, •O₂⁻, and •OH under one−/two-photon excitation. Furthermore, <strong>2d</strong> effectively overcame the tumor hypoxic microenvironment and exhibited strong one−/two-photon photodynamic activities against HT29 cells (IC₅₀s = 0.18–0.56 μM, PIs = 88–263). Additionally, <strong>2d</strong> could significantly induce cancer cell apoptosis <em>via</em> reducing Bcl-2 and increasing Bax/Cleaved-caspase-3, and simultaneously promote programmed necrosis through boosting P-MLKL and P-RIPK1/3 expression. <em>In vivo</em> experiments substantiated that <strong>2d</strong> powerfully suppressed colonic tumor growth under one−/two-photon irradiation (suppression rates 77–91 %). Therefore, this work may provide an effective approach for designing novel β-carboline/quinolinium photosensitizers and present a promising prospect in the field of one−/two-photon tumor photodynamic therapy.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108538"},"PeriodicalIF":4.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and optimization of ibuprofen derivatives as the NF-κB/iNOS pathway inhibitors for the treatment of ulcerative colitis","authors":"Chao Lin ,&nbsp;Zhong-Sheng Li ,&nbsp;Zhan-Wei Dong ,&nbsp;Xiao-Yi Wu ,&nbsp;Min Ye ,&nbsp;Ke Li ,&nbsp;Zhen Jin ,&nbsp;Wei Wang ,&nbsp;You-Zhi Tang","doi":"10.1016/j.bioorg.2025.108506","DOIUrl":"10.1016/j.bioorg.2025.108506","url":null,"abstract":"<div><div>In this study, a series of novel ibuprofen (<strong>Ibu</strong>) hybrid molecules with aminothiazole heterocycles were designed, synthesized and evaluated for their anti-inflammatory potency <em>in vitro</em> and <em>in vivo</em>. Among all these derivatives, compounds <strong>6</strong> and <strong>8</strong> effectively inhibited the production of NO (with 87 %, 79 % NO-inhibitory rates, respectively) with minimal cytotoxic effect in RAW 264.7 macrophages. Anti-inflammatory mechanism studies revealed that representative compound <strong>6</strong> dose-dependently inhibited pro-inflammatory cytokines by blocking the activation of NF-κB signaling pathway in LPS stimulated RAW 264.7 macrophages. <em>In vivo</em> experiments showed that 10 mg/kg compound <strong>6</strong> had a good improvement effect in DSS-induced mouse acute colitis compared to <strong>Ibu</strong>. Our findings will provide new insights into the development of new drugs with anti-inflammatory functions.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108506"},"PeriodicalIF":4.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}