Bioorganic Chemistry最新文献

{"title":"Isomeric 2-isobutylmalate derivatives with anti-pulmonary fibrosis effects from the leaves of Bletilla striata via LC-MS/MS-based molecular networking","authors":"Ming Zhou ,&nbsp;Si Liu ,&nbsp;Fang Yuan ,&nbsp;Jun Li ,&nbsp;Mengchen Zhou ,&nbsp;Junfeng Huang ,&nbsp;Yanjun Zhang ,&nbsp;Qiong Liang","doi":"10.1016/j.bioorg.2025.108351","DOIUrl":"10.1016/j.bioorg.2025.108351","url":null,"abstract":"<div><div>Based on the LC-MS/MS molecular networking strategy, nine undescribed 2-isobutylmalate derivatives, namely bletistrosides M–U (compounds <strong>1</strong>–<strong>7</strong>, <strong>9</strong>, and <strong>11</strong>), together with two known analogues (compounds <strong>8</strong> and <strong>10</strong>), were isolated and identified from the leaves of <em>Bletilla striata</em>. Their structures with absolute configurations were deduced from spectroscopic data, acidic hydrolysis, and comparison with reported compounds. Compounds <strong>1</strong>/<strong>2</strong>, <strong>3</strong>/<strong>4</strong>, <strong>5</strong>/<strong>6</strong>, and <strong>7</strong>/<strong>8</strong> represented four pairs of <em>Z</em>/<em>E</em> isomers regarding cinnamoyl groups, and each pair underwent interconversion under UV radiation at 254 nm. Biologically, compounds <strong>1</strong>, <strong>2</strong>, and <strong>10</strong> exhibited anti-pulmonary fibrosis effects against bleomycin-stimulated cell injury in A549 cells. Further investigations demonstrated that the anti-pulmonary fibrosis potential of <strong>2</strong> was related to the inhibition of apoptosis and epithelial-mesenchymal transition by blocking the Bax/Bcl-2, TGF-<em>β</em>1/Smad2/3, and PI3K/AKT signaling pathways, while concurrently enhancing the Nrf2 signaling pathway.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"159 ","pages":"Article 108351"},"PeriodicalIF":4.5,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673034","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":"Anticancer potential of Bellardia trixago quantum dots: Cytotoxic effects on various cancer cell lines","authors":"Erdi Can Aytar ,&nbsp;Zeynep Betul Sarı ,&nbsp;Muhammet Emin Sarı ,&nbsp;Alper Durmaz ,&nbsp;Emine Incilay Torunoğlu ,&nbsp;Abidin Gümrükçüoğlu ,&nbsp;Gamze Demirel","doi":"10.1016/j.bioorg.2025.108340","DOIUrl":"10.1016/j.bioorg.2025.108340","url":null,"abstract":"<div><div>This study investigates the synthesis, characterization, and anticancer effects of carbon quantum dots (CQDs) derived from <em>Bellardia trixago</em>. The CQDs were analyzed using Transmission Electron Microscopy (TEM), X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Photoelectron Spectroscopy (XPS). TEM results revealed that the CQDs have a spherical morphology and exhibit a layered structure. XRD analysis showed a graphite-like crystalline structure, while FTIR and XPS studies confirmed the presence of OH, C<img>C, and C<img>O functional groups on the surface. The biological activity of CQDs demonstrated selective cytotoxicity, inducing significant cell death in cancer cells while exhibiting low toxicity in healthy cells. More pronounced morphological changes were observed in HEp-2 and SaOS-2 cells, while HEK-293 cells showed negligible changes. These findings suggest that quantum dots could serve as a potential alternative for cancer treatment.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"158 ","pages":"Article 108340"},"PeriodicalIF":4.5,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143591264","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":"Structurally diverse sesquiterpenes with anti-leukemia activity from the rare medicinal plant Liriodendron chinense","authors":"Yu-Hang He ,&nbsp;Hong Xiang ,&nbsp;Zi-Jie Long ,&nbsp;Ze-Xin Jin ,&nbsp;Jin-Feng Hu ,&nbsp;Yi-Cheng Mao ,&nbsp;Juan Xiong","doi":"10.1016/j.bioorg.2025.108341","DOIUrl":"10.1016/j.bioorg.2025.108341","url":null,"abstract":"<div><div>A further phytochemical investigation on the branches and leaves of <em>Liriodendron chinense</em>, a rare medicinal and ornamental plant endemic to China, yielded thirty-four sesquiterpenes with diverse skeletons. The isolated compounds comprise 12 new naturally occurring sesquiterpenoids (<strong>1</strong>−<strong>12</strong>) and 22 known analogues (<strong>13</strong>–<strong>34</strong>). The new structures were elucidated by spectroscopic data analyses, and their absolute configurations (except for <strong>10</strong>) were determined by electronic circular dichroism spectra, quantum-chemical calculations, and X-ray crystallography. Among them, liriochinolide A (<strong>1</strong>) is a rare chlorine-substituted germacrane-type sesquiterpenoid from the terrestrial plants. Bioassay evaluations revealed that most of the isolates exhibited remarkable cytotoxicity against three human leukemia cell lines (MV-4-11, HL-60 and Raji), with IC₅₀ values ranging from 2.27 to 9.69 μM. Further exploration of anti-leukemia mechanism demonstrated that the bioactive compounds <strong>5</strong>, <strong>8</strong>, and <strong>18</strong> significantly induced the cell apoptosis, which was associated with down-regulation of the anti-apoptotic proteins BCL-2 and MCL-1.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"158 ","pages":"Article 108341"},"PeriodicalIF":4.5,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143591263","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 development of a bright NIR fluorescent probe for selective HSA detection in human blood serum and urine","authors":"Arindam Mondal,&nbsp;Subrata Dutta","doi":"10.1016/j.bioorg.2025.108356","DOIUrl":"10.1016/j.bioorg.2025.108356","url":null,"abstract":"<div><div>Human serum albumin (HSA), an important human blood protein, plays a critical role in maintaining osmotic pressure and facilitating the transport of various substances. Abnormal HSA levels are associated with diseases like kidney disease, heart problems, diabetes, and liver damage, necessitating the development of accurate methods for HSA detection. This paper describes the design, synthesis, and evaluation of four BODIPY-based near-infrared (NIR) fluorescent probes (BD1–BD4) for the selective detection of HSA. Among the synthesized probes, BD1 demonstrated exceptional sensitivity and specificity, exhibiting a 147-fold fluorescence enhancement at 660 nm (λ_ex = 600 nm) with a Stokes shift of 60 nm. The probe achieved a low detection limit of 9.5 nM, enabling the effective quantification of HSA in complex biological samples such as human blood serum and artificial urine. Competitive binding studies using ibuprofen confirmed that BD1 binds selectively to binding site II of HSA, which was further supported by a molecular docking study. Additionally, BD1 demonstrated HSA detection with a high recovery rate in artificial urine.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"159 ","pages":"Article 108356"},"PeriodicalIF":4.5,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611680","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":"Amoebicidal thymol analogues against brain-eating amoeba, Naegleria fowleri","authors":"Meriam Ben Youssef ,&nbsp;Amani Omrani ,&nbsp;Ines Sifaoui ,&nbsp;Eduardo Hernández-Álvarez ,&nbsp;Javier Chao-Pellicer ,&nbsp;Isabel L. Bazzocchi ,&nbsp;Hichem Sebai ,&nbsp;José E. Piñero ,&nbsp;Ignacio A. Jimenez ,&nbsp;Jacob Lorenzo-Morales","doi":"10.1016/j.bioorg.2025.108346","DOIUrl":"10.1016/j.bioorg.2025.108346","url":null,"abstract":"<div><div><em>Naegleria fowleri</em>, known as the brain-eating amoeba, is the pathogen parasite that causes primary amoebic meningoencephalitis. None of the currently available therapies are fully effective, mainly due to the inefficacy of pharmacotherapy. In this regard, natural products and related compounds represent a promising strategy for amoebicidal drug discovery. Herein, a series of eight monoterpene phenol derivatives of thymol bearing ester, carbonate, or carbamate moieties were prepared, and screened as potential amoebicidal agents on <em>N. fowleri</em>. The cytotoxicity of these compounds on murine macrophages cell line J774 was also evaluated to assess their selectivity. Compounds <strong>3</strong>, <strong>4</strong>, <strong>7</strong> and <strong>8</strong> showed significant activity against the <em>N. fowleri</em> trophozoite. Moreover, 4-nitrophenyl thymyl carbonate <strong>8</strong> displayed the highest potency, showing IC₅₀ values of 22.87 and 25.16 μM against <em>N. fowleri</em> trophozoite and cyst stages, respectively, coupled with low cytotoxicity on a mammal cell line. Furthermore, mechanism of action studies revealed that derivative <strong>8</strong> triggered programmed cell death via cytosolic calcium accumulation, mitochondrial alteration, membrane damage, chromatin condensation, and ROS accumulation. In addition, the <em>in-silico</em> ADME analysis indicated that derivative <strong>8</strong> exhibits exceptional drug-likeness meeting all the pharmacokinetic criteria. These results highlight derivative <strong>8</strong> as a promising amoebicidal agent to develop new drugs for the treatment of <em>Naegleria</em> infections.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"159 ","pages":"Article 108346"},"PeriodicalIF":4.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642820","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":"Unusual chaetoglobosins and a new type of ferroptosis inducer from an endophytic fungus Chaetomium sp. UJN-EF006","authors":"Yin-Yin Wang ,&nbsp;Yu-Song Wang ,&nbsp;Jun-Jiang Li ,&nbsp;Ze-Yi Wan ,&nbsp;Hua Zhang","doi":"10.1016/j.bioorg.2025.108342","DOIUrl":"10.1016/j.bioorg.2025.108342","url":null,"abstract":"<div><div>Seven unreported chaetoglobosin-type alkaloids, namely brachaetoglobosin A (<strong>1</strong>), chaetochalasins B<img>F (<strong>2</strong>–<strong>6</strong>) and armochaeglobine C (<strong>7</strong>), together with the formerly described cytoglobosin C (<strong>8</strong>) and chaetoglobosin E (<strong>9</strong>), were obtained from an endophytic fungus <em>Chaetomium</em> sp. UJN-EF006 isolated from the leaves of <em>Vaccinium bracteatum</em>. Their structures were characterized through various spectral techniques including MS, NMR, X-ray crystallography and electronic circular dichroism. Also, this is only the second record of novel chaetochalasin and armochaeglobine skeletons of the cytochalasin super family, after 27 and 10 years of the first report, respectively. Compound <strong>9</strong> showed significant cytotoxic effect against two human tumor cell lines (MDA-MB231 and A549) and was identified as a new type of ferroptosis inducer (toward A549 cells) that could be used as a molecular tool in future related research.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"158 ","pages":"Article 108342"},"PeriodicalIF":4.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580215","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":"Gold nanoparticles-based targeted delivery of rapamycin and Olaparib to breast cancer: An in vitro and in vivo approach","authors":"Mamatha Julappagari ,&nbsp;Shagufta Haque ,&nbsp;Sanchita Tripathy ,&nbsp;Swapnali Londhe ,&nbsp;Arti Patel ,&nbsp;Rajkumar Banerjee ,&nbsp;Chitta Ranjan Patra","doi":"10.1016/j.bioorg.2025.108322","DOIUrl":"10.1016/j.bioorg.2025.108322","url":null,"abstract":"<div><div>Triple negative form of breast cancer (abbreviated as TNBC) is considered as the most aggressive form causing high mortality worldwide. Different treatment modalities such as chemotherapy, surgery, hormonal therapy and radiation therapy are employed for eliminating breast cancer, which are associated with many limitations. Therefore, considering the significance of metal nanoparticles in the biomedical sector, especially gold nanoparticles, in the current manuscript, we have designed and developed a combinatorial approach for synthesizing two types of gold (Au) nanoformulations (Au-Dex-MUA-Rapa, Au-Dex-MUA-Ola) using 11-mercaptoundecanoic acid (MUA), dexamethasone (Dex) (glucocorticoid receptor targeted molecule) along with rapamycin (Rapa: inhibitor of mTOR) or olaparib (Ola: inhibitor of PARP) against TNBC. These gold nanoformulations were characterized thoroughly using several analytical techniques such as TEM, spectroscopy, DLS, HPLC and ICPOES. The <em>in vitro</em> MTT assays (normal cells: HEK-293 and CHO) and <em>ex vivo</em> CAM assay displays the biocompatible properties of the conjugated gold nanoformulations. Further, the anticancer properties of the conjugated gold nanoformulations in TNBC cells (MDA-MB-231) were evaluated through several <em>in vitro</em> experiments along with plausible mechanism of action. The intraperitoneal administration of gold nanoformulations into the breast tumor bearing BALB/c mice inhibits the tumor growth and increases their survivability. Additionally, we have investigated the plausible mechanistic studies behind the anticancer properties of the conjugated gold nanoformulations. Finally, we have found the non-toxic nature of these nanoformulations at therapeutic dose. Considering the above results, the conjugated gold nanoformulations could be used as an alternative therapeutic strategy for the treatment of breast carcinoma in near future.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"158 ","pages":"Article 108322"},"PeriodicalIF":4.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143591265","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":"Structure-based molecular hybridization design and synthesis of Keap1-Nrf2 inhibitors for anti-inflammatory treatment","authors":"Xiuting Qin ,&nbsp;Ruilin Hou ,&nbsp;Zhuo Qu ,&nbsp;Jianqiang Yu ,&nbsp;Wannian Zhang ,&nbsp;Hao Ma ,&nbsp;Chunlin Zhuang","doi":"10.1016/j.bioorg.2025.108350","DOIUrl":"10.1016/j.bioorg.2025.108350","url":null,"abstract":"<div><div>The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway stands as a pivotal mechanism in defending against oxidative stress damage and related inflammation. Blocking the Keap1-Nrf2 protein-protein interaction (PPI) offers a promising therapeutic approach for treating diseases related to oxidative stress and inflammation. Our group previously reported NXPZ-2, a naphthalene sulfonamide derivative targeting Keap1, which effectively inhibits the Keap1-Nrf2 PPI, thereby releasing Nrf2 to exert its anti-inflammatory and antioxidant effects. In the present work, we employed a structure-based molecular hybridization strategy to design a series of novel naphthalene sulfonamides by combining NXPZ-2 with the Nrf2 activator dimethyl fumarate (DMF) or its analogues. Among these new derivatives, compound <strong>1c</strong>, specifically (<em>Z</em>)-4-((4-(N-(2-amino-2-oxoethyl)-N-(4-((N-(2-amino-2-oxoethyl)-4-methoxyphenyl)sulfonamide)naphthalen-1-yl) sulfamoyl)phenyl)amino)-4-oxobut-2-enoic acid, exhibited the highest PPI inhibitory activity, with a <em>K</em>_D2 value of 0.119 μM. In an LPS-induced RAW264.7 cell model, this compound mitigated LPS-induced cellular damage, suppressed the expression of pro-inflammatory cytokine TNF-α and IL-6, and significantly elevated the intracellular GSH and SOD enzyme activities. Furthermore, in an LPS-induced acute lung injury (ALI) mouse model, the compound demonstrated a remarkable ability to alleviate oxidative damage and inflammation in the lungs. In conclusion, this novel naphthalene sulfonamide represents a promising drug candidate for Keap1-targeting therapy in ALI. Molecular docking analysis revealed that the amide and maleic acid groups of <strong>1c</strong> facilitate strong interactions with the Kelch domain of Keap1, explaining the compound's preference for binding through hydrogen bonding and π-π stacking interactions.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"158 ","pages":"Article 108350"},"PeriodicalIF":4.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143591439","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":"Development of novel amino-benzenesulfonamide derivatives and their analogues as carbonic anhydrase inhibitors: Design, synthesis, anticancer activity assessment, and pharmacokinetic studies using UPLC-MS/MS","authors":"Khaled A. Elsayad ,&nbsp;Ghada F. Elmasry ,&nbsp;Sally T. Mahmoud ,&nbsp;Fadi M. Awadallah ,&nbsp;Simone Giovannuzzi ,&nbsp;Claudiu T. Supuran","doi":"10.1016/j.bioorg.2025.108335","DOIUrl":"10.1016/j.bioorg.2025.108335","url":null,"abstract":"<div><div>The present study outlines the design and synthesis of dual-tail analogues of SLC-0111 as carbonic anhydrase inhibitors (CAIs) targeting tumor isoforms IX and XII <strong>4a-h</strong> and <strong>5a-h</strong>, along with pharmacokinetic studies. The synthesized compounds were evaluated for their inhibitory activity against four carbonic anhydrase isoforms (hCA I, II, IX, and XII), revealing potent activity, particularly against hCA IX and XII. Notably, compounds <strong>4b</strong>, <strong>5a</strong>, and <strong>5b</strong> demonstrated strong inhibition of hCA IX with K_i values of 20.4, 12.9, and 18.2 nM, respectively, compared to acetazolamide (AAZ), which has a K_i of 25 nM. Additionally, compounds <strong>5a</strong>, <strong>5b</strong>, <strong>5c</strong>, and <strong>5d</strong> showed selective inhibition of hCA XII, with K_i values of 26.6, 8.7, 17.2, and 10.9 nM, respectively, relative to AAZ (K_i = 5.7 nM). Moreover, both series were tested for their anti-proliferative activity following the US-NCI protocol against a panel of more than fifty cancer cell lines. Compound <strong>5</strong><strong>h</strong> met the activity criteria and was automatically scheduled for further evaluation at five concentrations with 10-fold dilutions, revealing high toxicity toward leukemia and lower toxicity against melanoma. In addition, the MTT cytotoxicity assay was performed on <strong>5f, 5d</strong> and acetazolamide using WI-38 cells. Furthermore, an in vivo pharmacokinetic study was conducted using UPLC-MS/MS on the most potent derivative, <strong>5d</strong>, demonstrating a comparable pharmacokinetic profile compared to the reference drug acetazolamide. Furthermore, molecular docking prediction studies were conducted for the most active compounds, <strong>5d</strong> and <strong>5</strong><strong>h</strong>, to elucidate their interactions with the active site hot spots of the CA isoform.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"159 ","pages":"Article 108335"},"PeriodicalIF":4.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611678","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":"Benzo-α-pyrone-derived multitargeting actions to enhance the antibacterial performance of sulfanilamides against Escherichia coli","authors":"Yi-Xin Wang ,&nbsp;Hao-Ran Wang ,&nbsp;Jiang-Sheng Zhao ,&nbsp;Xun-Cai Yang ,&nbsp;Bo Fang ,&nbsp;Zhong-Lin Zang ,&nbsp;Rong-Xia Geng ,&nbsp;Cheng-He Zhou","doi":"10.1016/j.bioorg.2025.108339","DOIUrl":"10.1016/j.bioorg.2025.108339","url":null,"abstract":"<div><div>A novel class of benzopyrone-sulfanilamide hybrids was synthesized from phenols <em>via</em> multi-step reactions. Some prepared compounds effectively suppressed bacterial growth at low concentrations, and especially, sulfanilamide-hybridized 2-methyl-5-nitroimidazolyl benzopyrone <strong>11c</strong> exhibited significant inhibitory potency against <em>Escherichia coli</em> (MIC = 0.0022 mM), which was 11-fold more active than clinical norfloxacin. Furthermore, compound <strong>11c</strong> showed negligible hemolytic activity, low cytotoxicity and no drug resistance. Mechanistic studies indicated that the highly active <strong>11c</strong> disrupted bacterial membrane integrity, reduced metabolic activity, bound DNA grooves to inhibit replication without the ability to cleave DNA, and induced reactive oxygen species (ROS) accumulation, collectively leading to bacterial death. These results highlight the potential of sulfanilamide-hybridized benzopyrones as multitarget antibacterial agents, warranting further development to combat bacterial infections.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"158 ","pages":"Article 108339"},"PeriodicalIF":4.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580213","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}