Bioorganic Chemistry最新文献

{"title":"Cascade synthesis of miltirone derivatives via arylation, decarboxylation, and aromatization for their potential as antitumor agents","authors":"Huilian Huang ,&nbsp;Fucheng Yin ,&nbsp;Yonglei Zhang ,&nbsp;Zhongwen Luo ,&nbsp;Siyuan Wan ,&nbsp;Liangliang Ma ,&nbsp;Xiaobing Wang","doi":"10.1016/j.bioorg.2025.108488","DOIUrl":"10.1016/j.bioorg.2025.108488","url":null,"abstract":"<div><div>Miltirone is a valuable bioactive natural product isolated from the well-known Chinese herb Danshen. In this study, palladium-catalyzed C(sp³) − H arylation, decarboxylation and aromatization cascade approach are reported that allows the direct introduction of various aryl groups at the A-ring benzylic methylene of various miltirone substrates (<strong>CA2</strong> − <strong>CA31</strong>). The evaluation of the cytotoxic activity was performed against three human cancer cell lines. Among the synthesized compounds, the derivative <strong>CA7</strong> (IC₅₀ = 0.45 μM) exhibited excellent MDA-MB-231 cells inhibition activity. Derivative <strong>CA7</strong> inhibited MDA-MB-231 cells migration, significantly suppressed the colony formation downregulated mitochondrial membrane potential and induced reactive oxygen species accumulation leads to apoptosis of MDA-MB-231 cells. <strong>CA7</strong> with potential anticancer properties warranting further development.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108488"},"PeriodicalIF":4.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887214","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":"Isolation of recombinant HIV-1 Rev protein and investigation of a new class of benzimidazole inhibitors capability to disrupt Rev–RRE complex","authors":"Anastasia S. Zemskaya ,&nbsp;Albert F. Arutyunyan ,&nbsp;Daria K. Sherman ,&nbsp;Dmitry V. Yanvarev ,&nbsp;Alexey V. Shuvalov ,&nbsp;Lyudmila B. Kalnina ,&nbsp;Dmitry N. Kaluzhny ,&nbsp;Roman A. Novikov ,&nbsp;Pavel N. Solyev ,&nbsp;Vladimir T. Valuev-Elliston","doi":"10.1016/j.bioorg.2025.108487","DOIUrl":"10.1016/j.bioorg.2025.108487","url":null,"abstract":"<div><div>In the present study, an efficient method for the expression and purification of recombinant HIV Rev protein with a C-terminal hexahistidine tag was proposed. Noteworthy, this method circumvents the precipitation of the protein into inclusion bodies and their subsequent aggregation during purification. It does not necessitate denaturing isolation conditions, in contrast to currently widely used protocols. As a result, protocols for HIV Rev isolation have been developed allowing the production of non-aggregated Rev protein in a good yield, high purity, and free of bacterial RNA impurities. This high-purity result became possible due to high salt extraction buffer usage. Complementary [α-³²P]-labeled Rev response element (RRE) RNA has been synthesized and an inhibitor test system was developed based on Rev–RRE complex formation. We were able to reveal a novel class of potential Rev–RRE inhibitors based on dimeric benzimidazole derivatives and used those results to validate the testing system. The proposed protocols for screening and structure-activity relationship for new inhibitors of Rev binding to viral RNA broaden the scope of potential candidates for anti-HIV drug development.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108487"},"PeriodicalIF":4.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873255","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":"A novel hydroxytyrosol derivative HT-3 enhances antioxidant and neuroprotective activity through efficient molecular conjugation","authors":"Linjie Zhang ,&nbsp;Haopai Wei ,&nbsp;Taihe Han ,&nbsp;Suntao Shi ,&nbsp;Xiaopeng Zhang ,&nbsp;Xuezhao Shi ,&nbsp;Haixia Zhang ,&nbsp;Baoxin Zhang","doi":"10.1016/j.bioorg.2025.108484","DOIUrl":"10.1016/j.bioorg.2025.108484","url":null,"abstract":"<div><div>Molecular conjugation is a promising strategy for drug development, which could enhance the efficacy, selectivity, and bioavailability of high-potency compounds through precise structural modifications. Our previous studies demonstrated that hydroxytyrosol (HT) provides excellent neuroprotection in PC12 cells, which is derived from olive oil, and now widely used as a natural food additive. In this study, we rationally designed and synthesized a string of HT derivations by coupling caffeic acid skeletons, and found that <strong>HT-3</strong> exhibited the strongest antioxidant activity and superior neuroprotective efficacy via the Keap1/Nrf2/ARE pathway among the HT analogue. Additionally, nanoparticles of <strong>HT-3</strong> (<strong>HT-3</strong> NPs) were constructed for reducing toxicity and enhancing efficacy, which could enhance blood-brain barrier penetration, accelerate metabolism, and prolong brain retention in mice model of Parkinson's disease. This work would open a new avenue for further investigation of HT analogue.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108484"},"PeriodicalIF":4.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879405","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":"Designing novel tridentate iridium(III) complexes comprising functionalized benzothiazole ligands to improve anticancer activity by targeting mitochondria","authors":"Qin Zhou ,&nbsp;Xiao-Bin Zhang ,&nbsp;An-Li Liu ,&nbsp;Zhi-Gang Niu ,&nbsp;Gao-Nan Li ,&nbsp;Fa-Biao Yu","doi":"10.1016/j.bioorg.2025.108507","DOIUrl":"10.1016/j.bioorg.2025.108507","url":null,"abstract":"<div><div>In recent years, organo‑iridium anticancer agents have shown promising antitumor activity toward cancer cells. In this paper, two benzothiazole-based tridentate ligands, 2,2′-(5-<em>(tert</em>-butyl)-1,3-phenylene)bis(benzo[<em>d</em>]thiazole) (<strong>L</strong>_{<strong>1</strong>}) and 2,2′-(5-(methyl)-1,3-phenylene)bis(benzo[<em>d</em>]thiazole) (<strong>L</strong>_{<strong>2</strong>}), have been designed and synthesized, and then combined with 2,2′-bipyridine (bipy) and 1,10-phenanthroline (phen) ancillary ligands to form a series of novel [Ir(N^C^N)(N^N)Cl]⁺-type iridium(III) complexes (<strong>Ir1</strong>-<strong>Ir4</strong>). The phosphorescence properties of these complexes facilitate the visualization of their subcellular localization and interactions with other biomolecules. Among them, complex <strong>Ir2</strong> has the best cytotoxicity activity toward A549 cells and its antitumor activity was further evaluated. Laser confocal assay reveals that <strong>Ir2</strong> followed an energy-dependent cellular uptake mechanism and specifically accumulates in mitochondria (Pearson colocalization coefficient: 0.89). The anticancer mechanism has been explored through apoptosis, cell cycle arrest, western blotting (WB), reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) changes. The antitumor activity <em>in vivo</em> confirms that <strong>Ir2</strong> could effectively inhibit tumor growth with an inhibitory rate of 71.60 %, which is superior to cisplatin. To the best of our knowledge, <strong>Ir2</strong> is a rare example of [Ir(N^C^N)(N^N)Cl]⁺-type complexes as potential anticancer agents.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108507"},"PeriodicalIF":4.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873256","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":"S-adenosylmethionine inhibits non-small cell lung cancer and enhances chemosensitivity by targeting the P62/NF-κB axis and regulating autophagy and oxidative stress","authors":"Xuehang Jin ,&nbsp;Lvjun Zhang ,&nbsp;Chiqing Ying ,&nbsp;Long Yu ,&nbsp;Xuejing Guo ,&nbsp;Kailing Pan ,&nbsp;Dan Zhu ,&nbsp;Hui Chen","doi":"10.1016/j.bioorg.2025.108509","DOIUrl":"10.1016/j.bioorg.2025.108509","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Despite advances in targeted therapies and immunotherapy, which have improved survival rates, drug resistance and immune-related side effects continue to necessitate the development of new treatments. S-adenosylmethionine (SAM), a key metabolite in the methionine cycle, has indicated potential for cancer therapy and enhancing chemotherapy sensitivity. However, its effects on NSCLC remain undetermined. In our study, SAM inhibits NSCLC growth and enhances chemosensitivity both <em>in vitro</em> and <em>in vivo</em>. Mechanistic investigations revealed that SAM plays a significant regulatory role in autophagy and oxidative stress within NSCLC. Furthermore, we identified P62 as a critical target of SAM by constructing biotin-labeled SAM for immunocoprecipitation-mass spectrometry. Both <em>in vitro</em> and <em>in vivo</em> studies confirmed that P62 mediates SAM regulatory effects on NSCLC. Furthermore, by constructing truncated P62 expression plasmids for immunocoprecipitation experiments, we discovered that SAM inhibits the NF-κB signaling pathway by directly targeting the ZZ and TB domains of the P62 protein, thereby blocking autophagy and activating oxidative stress. These findings highlight SAM as a novel inhibitor of the P62/NF-κB axis and suggest that SAM could be a potential therapeutic agent for NSCLC.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"160 ","pages":"Article 108509"},"PeriodicalIF":4.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868978","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":"Genome-guided discovery of coublibactins from Nocardia coubleae and their gallium complexes with potent antileukemic activity","authors":"Qiaoqiao Tao ,&nbsp;Teng Cai ,&nbsp;Yang Xiao ,&nbsp;Tao Han ,&nbsp;Ling Shen ,&nbsp;Chang Cheng ,&nbsp;Shouying Xu ,&nbsp;Aiying Li ,&nbsp;Peng Zhang ,&nbsp;Jiachun Chen ,&nbsp;Yonghui Zhang ,&nbsp;Qingyi Tong ,&nbsp;Xiaofeng Cai","doi":"10.1016/j.bioorg.2025.108508","DOIUrl":"10.1016/j.bioorg.2025.108508","url":null,"abstract":"<div><div>The pursuit of highly effective and selective anticancer drugs remains a critical challenge. Metal-based complexes, particularly gallium-containing compounds, offer promising therapeutic avenues due to their unique mechanisms of action. To identify novel scaffolds for such complexes, we performed a comprehensive genomic analysis of <em>Nocardia</em> species, revealing the prevalence of siderophore biosynthetic gene clusters, including the highly conserved nocobactin NA-like clusters. From <em>N. coubleae</em> DSM 44960, we isolated three new siderophores, coublibactins A–C (<strong>1</strong>–<strong>3</strong>), along with eight congeners (<strong>4</strong>–<strong>11</strong>) with known planar structures, all characterized by exceptional iron-binding affinity. Subsequent gallium substitution yielded gallium complexes (Ga-<strong>1</strong>–<strong>11</strong>). Among these, Ga-<strong>6</strong> exhibited significant anticancer activity against human acute promyelocytic leukemia NB4 cells with IC₅₀ value of 1.35 μM. Pharmacological studies showed that Ga-<strong>6</strong> induces cell cycle arrest and apoptosis in NB4 cells. Our findings revealed microbial siderophores as promising scaffolds for the design of next-generation metal-based anticancer therapeutics, particularly gallium-based agents.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"160 ","pages":"Article 108508"},"PeriodicalIF":4.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868977","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":"Synthesis, structure activity relationship and biological evaluation of indole sulfonohydrazide derivatives as antagonists of P2Y1 and P2Y6 receptors","authors":"Abdul Hameed ,&nbsp;Ismat Nawaz ,&nbsp;Salman Alrokayan ,&nbsp;Tajamul Hussain ,&nbsp;Jamshed Iqbal","doi":"10.1016/j.bioorg.2025.108499","DOIUrl":"10.1016/j.bioorg.2025.108499","url":null,"abstract":"<div><div>The P2Y receptors play a significant role in regulating various physiological functions, such as neurotransmission and inflammatory response. They are also considered promising therapeutic targets for the treatment and prevention of conditions like neurological disorders, pain, cardiovascular diseases, thrombosis, and cancer. Active research is ongoing to identify antagonists of P2Y receptor. Although extensive research has been conducted on P2Y receptors inhibitors, only a limited number of P2Y receptors antagonists have been identified and approved by regulatory authority. In the current research, new indole sulfonohydrazide derivatives <strong>(3a</strong>-<strong>3</strong> <strong>k)</strong> were synthesized in good yield. Based on toxicity assays performed on <em>h</em>-1321 N1 astrocytoma cell line, these low molecular weight compound showed a safe toxicity profile. The synthesized derivatives were also screened against <em>t</em>P2Y1 and <em>r</em>P2Y6 receptors using a calcium mobilization assay. The results showed that compounds <strong>3a</strong>, <strong>3b</strong>, <strong>3</strong> <strong>h</strong> and <strong>3</strong> <strong>k</strong> were potent against <em>t</em>P2Y1 with IC₅₀ values of 9.91 ± 1.01 μM, 3.49 ± 0.31 μM, 9.72 ± 0.82 μM, and 6.14 ± 0.17 μM, respectively. Additionally, three compounds, <em>i.e.</em>, <strong>3d</strong>, <strong>3f</strong>, and <strong>3</strong> <strong>h</strong>, exhibited potency against <em>r</em>P2Y6 with IC₅₀ value of 9.22 ± 1.10 μM, 16.25 ± 0.27 μM, and 1.89 ± 0.11 μM, respectively. Molecular docking study was conducted to support the <em>in vitro</em> analysis, which revealed that the tested compounds showed favorable interaction with the amino acids of the target P2Y1 receptor, including Phe62, Phe66, Leu102, Thr103, Pro105, Ala106, Phe119 and Met123. An <em>in silico</em> pharmacokinetic study was also performed, which revealed that the synthesized compounds met all the criteria for favorable gastrointestinal absorption, indicating potential for oral bioavailability. The stability and reactivity of compounds were determined by using the Guassian09 programme in which the density functional theory (DFT) calculations were performed by using the B3LYP/SVP level.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"160 ","pages":"Article 108499"},"PeriodicalIF":4.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868980","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":"Proteolysis targeting chimera, molecular glue degrader and hydrophobic tag tethering degrader for targeted protein degradation: Mechanisms, strategies and application","authors":"Yanchang Pan ,&nbsp;Yuanjiang Wang ,&nbsp;Shaohua Gou","doi":"10.1016/j.bioorg.2025.108491","DOIUrl":"10.1016/j.bioorg.2025.108491","url":null,"abstract":"<div><div>Targeted protein degradation (TPD) represents a revolutionary approach to drug discovery, offering a novel mechanism that outperforms traditional inhibitors. This approach employs small molecule drugs to induce the ubiquitination and subsequent degradation of target protein <em>via</em> the proteasome or lysosomal pathways. Key strategies within TPD include proteolysis targeting chimeras (PROTACs), hydrophobic tag tethering degraders (HyTTDs), and molecular glue degraders (MGDs). PROTACs have been undergone clinical evaluations, MGDs have been used in the clinic, and HyTTDs have shown significant progress in cancer treatment. Each of these strategies presents unique advantages and approaches to target protein degradation. This review summarizes five years of research on PROTACs, HyTTDs, and MGDs, highlighting their design principles, advantages, limitations, and future challenges to provide clear guidance and in-depth insights for advancing drug development.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108491"},"PeriodicalIF":4.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881387","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":"Identification of CH2-linker modified desfluoroquinolone-aminopyrimidine hybrids to combat antibiotic-resistant gram-positive bacteria","authors":"Yue Hu ,&nbsp;Xinghua Xu ,&nbsp;Jiayi Chen ,&nbsp;Tao Xu ,&nbsp;Peng Cui ,&nbsp;Renhua Fan ,&nbsp;Qiuqin He","doi":"10.1016/j.bioorg.2025.108496","DOIUrl":"10.1016/j.bioorg.2025.108496","url":null,"abstract":"<div><div>The increasing prevalence of antibiotic-resistant bacterial infections has emerged as a major public health crisis, necessitating an urgent need for the development of new antimicrobial agents. In this manuscript, structural modifications were conducted on the CH₂ linker of the antibacterial desfluoroquinolone-aminopyrimidine hybrids that we had previously obtained, resulting in compounds <strong>A7</strong>, <strong>B1</strong>, and <strong>D6</strong>. These three compounds exhibited potent activity against a panel of antibiotic-resistant Gram-positive bacteria, including fluoroquinolone-resistant <em>Staphylococcus aureus</em>, linezolid-resistant <em>Staphylococcus aureus</em>, vancomycin-intermediate <em>Staphylococcus aureus</em> (VISA), and vancomycin-resistant <em>Enterococcus faecium</em>. Particularly, despite their structural similarity to classical quinolones, compounds <strong>A7</strong>, <strong>B1</strong>, and <strong>D6</strong> exhibited no cross-resistance with ciprofloxacin. Additionally, the difluorinated CH₂-linker modified compound demonstrated enhanced metabolic stability. These promising results encourage us to move forward to the next phase of structural optimization, with a specific focus on reducing mammalian cytotoxicity.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108496"},"PeriodicalIF":4.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873257","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":"Diterpenes as nitric oxide secretion inhibitors from Kaempferia koratensis rhizomes","authors":"Patcharin Kongwaen ,&nbsp;Jutatip Boonsombat ,&nbsp;Sanit Thongnest ,&nbsp;Rapeepat Sangsuwan ,&nbsp;Nedsai Uddin Babar ,&nbsp;Tawit Suriyo ,&nbsp;Chatphorn Theppitak ,&nbsp;Kittipong Chainok ,&nbsp;Jutamaad Satayavivad ,&nbsp;Chulabhorn Mahidol ,&nbsp;Somsak Ruchirawat","doi":"10.1016/j.bioorg.2025.108490","DOIUrl":"10.1016/j.bioorg.2025.108490","url":null,"abstract":"<div><div><em>Kaempferia koratensis</em> Picheans. (Zingiberaceae), known locally as “Proa Korat” or “Wan Proa Khao,” is native to northeastern Thailand where it is widely used for its aromatic properties in the local cuisine. Given its potential for expanded applications in traditional medicines, and for foods and food supplements derived from certain <em>Kaempferia</em> species, this study focused on the metabolites of <em>K. koratensis</em> rhizomes and evaluated their <em>in vitro</em> anti-inflammatory properties. Eight new isopimarane diterpenoids were isolated, including five koratones A–E, two koratanes C and D, and a bisditerpenoid, named as koratensin, together with six known isopimarane diterpenoids. The anti-inflammatory properties were evaluated by inhibiting nitric oxide production, with curcumin used as a positive control. The results revealed that koratone B was the most potent isolate at 25 μg/mL with 36.54 ± 0.79 % inhibition and koratane D at 50 μg/mL with 58.85 ± 4.12 % inhibition. Molecular docking of koratone B suggested the inhibitory effect was due to an affinity for hydrogen bonding at the active site of iNOS. The physicochemical and pharmacokinetic properties of koratone B were calculated. These findings indicate that selected isopimarane diterpenoids from <em>K. koratensis</em>, such as koratone B, merit further developmental consideration to potentiate the observed biological response.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"160 ","pages":"Article 108490"},"PeriodicalIF":4.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859582","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}