Bioorganic & Medicinal Chemistry最新文献

{"title":"Discovery of a potent C20-oxime pachysandra alkaloid analogue promising for treatment of hepatocellular carcinoma","authors":"Chen-Liang Zhao ,&nbsp;Wen-Wen Zhang ,&nbsp;Jin-Feng Zhao ,&nbsp;Jiang-Hai Ye ,&nbsp;Peng Wei ,&nbsp;Juan Zou ,&nbsp;Kang He","doi":"10.1016/j.bmc.2025.118324","DOIUrl":"10.1016/j.bmc.2025.118324","url":null,"abstract":"<div><div>The Miao medicine “Sanliangyin” is derived from the root of the <em>Sarcococca ruscifolia</em> (genus Sarcococca, family Buxaceae), which has been commonly used in Miao regions to treat malignant tumors. Previous research by our group has identified pachysandra alkaloids as the primary active ingredients in this plant, which exhibited anti-tumor properties. However, the low structural diversity and moderate activity of the isolated alkaloids hampered their clinical application. One of the effective strategies to address these challenges is the introduction of bioactive pharmacophores, leading to the development of natural product-pharmacophore hybrids (NPPH) with enhanced drug properties. To the best of our knowledge, oxime groups that introduced into natural products usually have enhanced the anti-cancer activity. Therefore, to develop more potent pachysandra alkaloid analogues with low toxicity, we synthesized a series of derivatives (<strong>7a</strong>-<strong>7</strong> <strong>g</strong>) to increase their structure diversity by introducing various anilines at C-3 and oxime at C-20 positions of epiandrosterone. Using the CCK-8 assay, we found that the IC₅₀ values of the pachysandra alkaloid derivatives against HepG2 liver cancer cells ranged from 0.127 to 1.536 μM. Further evaluation on THP-1 cells showed that, at a concentration of 12.50 μM, the cytotoxicity of the seven compounds ranged from 46.06 % to 100.00 %. Based on cell viability and cytotoxicity assay, we found that compound <strong>7a</strong> exhibited the strongest activity against liver cancer cells while showing the lowest toxicity. Network pharmacology and molecular dynamics simulation studies revealed that compound <strong>7a</strong> had a strong correlation and good binding affinity with the JAK2/STAT3 signaling pathway. Further mechanism studies have shown that compound <strong>7a</strong> could inhibit migration, induce mitochondrion-mediated apoptosis, thereby suppressing cell proliferation in HepG2 cells through regulation of Bcl-2 family proteins and the JAK2/STAT3 signaling pathway.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118324"},"PeriodicalIF":3.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679099","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}

{"title":"Inhibition of cytochrome bd oxidase in Mycobacterium tuberculosis by benzothiazole amides","authors":"Rohit Kumar ,&nbsp;Arnab Roy ,&nbsp;Nitin P. Kalia ,&nbsp;Deepak K. Sharma","doi":"10.1016/j.bmc.2025.118323","DOIUrl":"10.1016/j.bmc.2025.118323","url":null,"abstract":"<div><div>Cytochrome <em>bd</em> (Cyt-<em>bd</em>) oxidase, a key enzyme in the <em>Mtb</em> respiratory chain, is particularly crucial for ATP synthesis when the primary cytochrome <em>bc</em>_<em>1</em><em>:aa</em>_<em>3</em> (Cyt-<em>bc</em>_<em>1</em><em>:aa</em>_<em>3</em>) complex is compromised. There are several reported inhibitors of the Cyt-<em>bd</em> oxidase, predominantly featuring quinoline and quinazoline scaffolds. This study explores benzothiazole amides as potential inhibitors of Cyt-bd oxidase for their ability to deplete ATP in the presence of the Cyt-<em>bc</em>_<em>1</em><em>:aa</em>_<em>3</em> inhibitor Q203. These compounds demonstrated significant bactericidal activity against both replicating and non-replicating <em>Mtb</em> strains in this combined approach. Methylene blue assays confirmed their ability to inhibit oxygen consumption, validating their Cyt-<em>bd</em> inhibitory mechanism. Moreover, cytotoxicity studies indicated low toxicity and high selectivity for bacterial cells over mammalian cells. Molecular docking studies elucidated favourable binding interactions with the Cyt-<em>bd</em> protein, while <em>in silico</em> ADME profiling suggested promising pharmacokinetic properties. These results highlight the potential of benzothiazole amides as promising candidates for anti-TB drug development, specifically targeting the Cyt-<em>bd</em> oxidase. Future research will focus on further optimising these compounds and conducting preclinical evaluations to realize their clinical potential as adjuncts in TB therapy.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118323"},"PeriodicalIF":3.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696510","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}

{"title":"Design, synthesis, kinetic analysis, molecular docking, and mechanistic studies of novel coumarin-oxadiazole derivatives as α-glucosidase and PTP1B inhibitors","authors":"Yan Zhao ,&nbsp;Zhiyun Peng ,&nbsp;Guangcheng Wang","doi":"10.1016/j.bmc.2025.118321","DOIUrl":"10.1016/j.bmc.2025.118321","url":null,"abstract":"<div><div>α-Glucosidase and protein tyrosine phosphatase 1B (PTP1B) are crucial targets for diabetes treatment, and inhibiting their activity simultaneously can delay the absorption of carbohydrates and enhance insulin sensitivity by modulating the insulin signaling pathway. In this study, novel coumarin-oxadiazole derivatives were prepared by targeting these enzymes. Among them, compound <strong>5j</strong> exhibited dual inhibitory activity against α-glucosidase and PTP1B with IC₅₀ values of 30.57 ± 0.22 μM and 7.58 ± 1.96 μM, respectively. Kinetic experiments indicated it was a mixed-type α-glucosidase inhibitor. Ultraviolet and infrared spectroscopy experiments showed it could induce conformational changes in α-glucosidase, while circular dichroism spectroscopy experiments demonstrated the ability to alter the conformations of both α-glucosidase and PTP1B. Molecular docking results revealed that the compound could embed into the active pockets of both enzymes. The sucrose-loading test showed it could reduce post-prandial blood glucose in vivo, and it had low cytotoxicity in normal cells. In conclusion, as a multi-target inhibitor, compound <strong>5j</strong> shows great potential in the exploration and innovation of novel anti-hyperglycemic medications.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118321"},"PeriodicalIF":3.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696509","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}

{"title":"Rapid detection of hydrogen sulfide utilizing dinitrophenyl ether-based fluorescent probes incorporating aldehyde functional groups","authors":"Yuting Du,&nbsp;Hongliang Wang,&nbsp;Sanhu Zhao,&nbsp;Minmin Guo,&nbsp;Xiaojing Yang","doi":"10.1016/j.bmc.2025.118322","DOIUrl":"10.1016/j.bmc.2025.118322","url":null,"abstract":"<div><div>Hydrogen sulfide (H₂S) plays a crucial role in the regulation of various physiological processes within living organisms, including cell signaling, vascular tone modulation, and the inflammatory response. The real-time detection and visualization of H₂S levels in practical samples hold significant importance for biological analysis. In this study, 3-(benzo[<em>d</em>]thiazol-2-yl)-5-bromo-2-(2,4-dinitrophenoxy)benzaldehyde (<strong>DTBH</strong>) was designed and synthesized based on the mechanism of excited state intramolecular proton transfer (ESIPT). The probe employs a 2,4-dinitrophenyl ether with an ortho-aldehyde group as the reaction site to test H₂S. As a result, it exhibits an ultrafast response to H₂S within only 5 s and demonstrates high absolute fluorescence quantum yield (Φfl) up to 17.63 %. Moreover, <strong>DTBH</strong> interacts with H₂S to release its precursor <strong>DTB</strong>, which leads to a marked enhancement in fluorescence emission with 542 nm. <strong>DTBH</strong> shows high sensitivity and excellent selectivity for H₂S over various other analytes. Significantly, the biological imaging investigations in cells demonstrated that <strong>DTBH</strong> could image endogenous and exogenous H₂S and provide a promising method for the detection of H₂S in biological systems.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118322"},"PeriodicalIF":3.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679098","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}

{"title":"Design, synthesis, and antidiabetic activities of 5-methoxypyrimidine derivatives targeting GPR119 and DPP-4","authors":"Fukang Yang ,&nbsp;Sumei Shi ,&nbsp;Shaobing Cheng ,&nbsp;Huilan Li ,&nbsp;Mai Zhang ,&nbsp;Pei Hu ,&nbsp;Zunhua Yang ,&nbsp;Yuanying Fang","doi":"10.1016/j.bmc.2025.118318","DOIUrl":"10.1016/j.bmc.2025.118318","url":null,"abstract":"<div><div>Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired insulin secretion. G protein-coupled receptor 119 (GPR119) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are promising therapeutic agents due to their complementary mechanisms in promoting insulin secretion and lowering blood glucose levels. In this study, we designed and synthesized a series of dual-target compounds by linking a 5-methoxypyrimidine-based GPR119 agonist to the DPP-4 inhibitors sitagliptin or vildagliptin via a flexible linker. Among them, compound <strong>27</strong> exhibited the strongest DPP-4 inhibitory activity with an inhibition rate of 97.5 % at 10 μM, along with potent GPR119 agonistic activity (EC₅₀ = 1.3 μM). In an oral glucose tolerance test (oGTT) in mice, compound <strong>27</strong> demonstrated significant glucose-lowering effects. These findings suggest that dual GPR119/DPP-4 targeting may offer a promising strategy for T2DM treatment.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118318"},"PeriodicalIF":3.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662398","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}

{"title":"Engineered B7-H3-targeted VHH-Fc fusion antibody demonstrates rapid tumor accumulation for infrared imaging in pancreatic cancer xenograft model","authors":"Xiaofei Mo ,&nbsp;Yinghui Xu ,&nbsp;Fengfeng Han ,&nbsp;Yuetao Wang ,&nbsp;Mingge Zhou ,&nbsp;Chen He","doi":"10.1016/j.bmc.2025.118319","DOIUrl":"10.1016/j.bmc.2025.118319","url":null,"abstract":"<div><div>B7 homolog 3 protein (B7-H3) represents a promising target for cancer diagnosis and therapy. Conventional B7-H3-targeting agents predominantly use IgG antibodies, which accumulate in tumors slowly due to their large molecular size (160–180 kDa, comprising a dimeric Fab-Fc structure), leading to an increased risk of peripheral side effects. In this study, a novel fusion antibody, A052, was developed, integrating the variable domain of a nanobody heavy chain (VHH) and the Fc domain of IgG1. This design preserves the fundamental structure of an antibody while reducing the molecular weight to 82 kDa. Evaluation through enzyme-linked immunosorbent assay, flow cytometry, and bio-layer interferometry revealed that A052 binds with a significantly higher affinity (KD = 77.2 pM) compared to the anti-B7-H3 IgG antibody, hBRCA84D, currently in clinical trials (KD = 8.13 nM). To compare the <em>in vivo</em> tumor accumulation properties, both A052 and hBRCA84D were labeled with Cy5 and assessed in a PANC-1 xenograft model using infrared imaging. A052-Cy5 showed faster tumor accumulation, reaching a visible tumor-background ratio (TBR) at 3 h post-injection, peaking at 1.97 at 24 h, and maintaining a TBR above 1.50 from 3 to 144 h. In contrast, hBRCA84D-Cy5 exhibited a TBR of 1.5 only between 48 and 110 h. These results suggest that VHH-Fc fusion antibodies, such as A052, offer a novel approach for B7-H3-targeted therapies, potentially facilitating rapid tumor distribution while minimizing peripheral toxicity risks.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118319"},"PeriodicalIF":3.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665666","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}

{"title":"Sulfadoxine derivatization through multicomponent reactions to obtain new antiplasmodial compounds","authors":"Angela Trejo ,&nbsp;Yunuen Avalos-Padilla ,&nbsp;Concepción Alonso ,&nbsp;Xavier Fernàndez-Busquets ,&nbsp;Carme Masdeu","doi":"10.1016/j.bmc.2025.118313","DOIUrl":"10.1016/j.bmc.2025.118313","url":null,"abstract":"<div><div>Malaria continues to have a devastating impact on disease-endemic countries. Despite significant advances have been achieved, the discovery and development of new drugs capable to avoid resistances remains a challenge. In the same way, the difficulty and complexity of drug discovery processes only aggravates this situation. Nowadays, new strategies have appeared to minimize the impact that resistance evolution entails, such as the improvement of pre-existing drugs through chemical adaptation. In this work, we describe the structural modification of the antimalarial drug sulfadoxine, to which the parasite has developed resistance. Since sulfadoxine displays in its structure an aniline residue capable of undergoing Povarov and Ugi multicomponent reactions, we have used these to obtain new derivatives. Specifically, in the Povarov reaction, sulfadoxine led to phenylquinoline-6-sulfonamide derivatives <strong>5</strong> when phenylstyrene was used as dienophile, or indeno[2,1-<em>c</em>]quinoline-2-sulfonamide derivatives <strong>8a</strong>, <strong>9</strong> and <strong>10</strong> when indene was used instead. On the contrary, when sulfadoxine was used as the residue amine in the Ugi reaction, derivatives <strong>13a</strong> and <strong>13b</strong> were obtained. Some of the synthesized derivatives, namely <strong>8a</strong>, <strong>13a</strong> and <strong>13b</strong> displayed a significantly higher in vitro antiplasmodial activity than the original sulfadoxine compound, and synergistic assays of these analogues in combination with pyrimethamine showed improved efficacy compared to sulfadoxine-pyrimethamine.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118313"},"PeriodicalIF":3.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144670595","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}

{"title":"Inhibition of amyloid fibrillization of amyloid β peptide by 4,7-disubstituted coumarin derivatives","authors":"Slávka Hamuľaková ,&nbsp;Adrián Gucký ,&nbsp;Roman Mezencev ,&nbsp;Mária Kožurková ,&nbsp;Zuzana Bednáriková ,&nbsp;Jozef Marek ,&nbsp;Ondřej Soukup ,&nbsp;Jiří Janoušek ,&nbsp;Zuzana Gažová","doi":"10.1016/j.bmc.2025.118302","DOIUrl":"10.1016/j.bmc.2025.118302","url":null,"abstract":"<div><div>Coumarins are well-known for their unique chemical structure and a wide range of biological effects. Various substituted coumarin-based compounds have emerged as promising candidates for the development of novel therapeutic agents against numerous diseases. This study was focused on the synthesis of new 4,7-disubstituted coumarin derivatives and investigation of their ability to inhibit the aggregation of Aβ₄₀ peptide, their cytotoxic effect on SH-SY5Y cells, their antioxidant properties, and their ability to penetrate the blood-brain barrier (BBB). The results revealed that the trihydroxy derivatives <strong>5a-c</strong> had been the most effective inhibitors of Aβ aggregation, promoting the formation of non-toxic, amorphous aggregates instead. Importantly, no significant decrease in the viability of SH-SY5Y neuroblastoma cells was observed after treatment with the studied coumarins. Among them, coumarin <strong>5a</strong> demonstrated the strongest antioxidant activity, while compound <strong>5b</strong> also exhibited good antioxidant properties, along with the best inhibition of Aβ aggregation (IC₅₀ = 13.5 μM), and adequate permeability across the blood-brain barrier. These findings suggest that compound <strong>5b</strong> is a promising candidate for further investigation in Alzheimer's disease pharmacotherapy.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118302"},"PeriodicalIF":3.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653610","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}

{"title":"Icariin modulates the tumor microenvironment in colorectal cancer by targeting M2 macrophage polarization via PI3K/AKT pathway","authors":"Yu Chen ,&nbsp;Yiming Qi ,&nbsp;Yulan Jiang ,&nbsp;Ying Li ,&nbsp;Shaoxue Yang ,&nbsp;Lu Wang ,&nbsp;Mingqian Li ,&nbsp;Kequn Chai ,&nbsp;Yifan Wang","doi":"10.1016/j.bmc.2025.118317","DOIUrl":"10.1016/j.bmc.2025.118317","url":null,"abstract":"<div><div>Colorectal cancer (CRC) progression is influenced by intricate interactions in the tumor microenvironment (TME), with M2-polarized macrophages being key players in enhancing tumor growth and suppressing the immune response. Icariin (ICA), a bioactive flavonoid isolated from <em>Epimedium brevicornu</em> Maxim., exhibits potential antitumor properties. Nevertheless, its role in modulating macrophage-mediated immunosuppression in CRC remains unclear. To assess ICA's effects on CRC malignancy within an M2-enriched microenvironment, we established a CRC cell/M2 macrophage co-culture system. ICA suppressed CRC cell proliferation, migration, and invasion in co-culture with M2 macrophages. M2 polarization markers and PI3K/AKT pathway modulation were analyzed by western blot and qRT-PCR. Mechanistic studies revealed that ICA inhibited M2 polarization and suppressed the phosphorylation of PI3K and AKT. In vivo validation utilized two models, an AOM/DSS-induced CRC model and a syngeneic CT26-WT implantation system, evaluating both tumor progression and macrophage phenotype alterations. We found that ICA attenuated tumor growth and reduced M2 macrophage infiltration. Collectively, these finding demonstrated that ICA suppressed M2 macrophage polarization via PI3K/AKT signaling pathway, thereby inhibiting CRC progression. This study reveals a previously unrecognized mechanism by which ICA inhibits CRC and demonstrates its potential as a promising therapeutic agent for CRC treatment.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118317"},"PeriodicalIF":3.3,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653011","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}

{"title":"The discovery of wheat-derived anticaries peptides by a ML-based computational strategy","authors":"Hai Guo ,&nbsp;Yunxiang Yu ,&nbsp;Zhou Zhang ,&nbsp;Chenchen Zhang ,&nbsp;Qian Fu ,&nbsp;Jie Zhang ,&nbsp;Wenjin Yan ,&nbsp;Jian Han ,&nbsp;Jinqi Huang","doi":"10.1016/j.bmc.2025.118303","DOIUrl":"10.1016/j.bmc.2025.118303","url":null,"abstract":"<div><div>This study proposes a machine learning-based peptide screening strategy for identifying wheat-derived peptides with anti-caries potential. By integrating multiple feature descriptors and algorithms (Random Forest, XGBoost), we constructed a Screening Funnel Model and identified a wheat-derived peptide AP-2 (FPVTWRWWKWW) as the prioritized candidate. Experimental validation demonstrated that AP-2 exhibits potent antibacterial activity against <em>Streptococcus mutans</em> (MIC = 4 μM), achieving rapid bactericidal effects through bacterial membrane disruption, and significantly inhibits biofilm formation at 1/2 × MIC concentration. AP-2 exhibited an extremely low hemolysis rate and demonstrated favorable stability in saliva within 1 h. In vivo, studies confirmed that AP-2 effectively prevents early caries formation in rats at low concentrations without inducing organ toxicity or oral microbiota dysbiosis. These results demonstrate the utility of machine learning in discovering wheat-derived anti-caries peptides and indicate that AP-2 represents a safe and effective candidate for clinical translation.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118303"},"PeriodicalIF":3.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634446","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}