Bioorganic Chemistry最新文献

{"title":"Issue TOC","authors":"","doi":"10.1016/S0045-2068(25)00411-0","DOIUrl":"10.1016/S0045-2068(25)00411-0","url":null,"abstract":"","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"160 ","pages":"Article 108531"},"PeriodicalIF":4.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886353","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":"Preparation of water-soluble imidazole-functionalized pillar[5]arenes: The activities of antibacterial and antioxidant, catalytic reduction of 4-nitrophenol","authors":"Keziban Atacan ,&nbsp;Alican Bahadır Semerci ,&nbsp;Nuray Güy ,&nbsp;Nubar Mammadova ,&nbsp;Mustafa Ozmen ,&nbsp;Ahmed Nuri Kursunlu","doi":"10.1016/j.bioorg.2025.108544","DOIUrl":"10.1016/j.bioorg.2025.108544","url":null,"abstract":"<div><div>Macrocyclic supramolecular materials such as pillar[<em>n</em>]arenes play a prominent role in enhancing antibacterial activity through host-guest interactions. Herein, the water-soluble pillar[5]arene imidazole-1 and pillar[5]arene imidazole-2 were prepared, and their structure and chemical compositions were analyzed through multiple characterization methods. Afterward, the prepared imidazole-functionalized pillar[5]arenes were examined for antibacterial activity against <em>Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, and Salmonella typhimurium</em> bacteria. Also, the antioxidant activities of the prepared imidazole-functionalized pillar[5]arenes were investigated using 2,2-Diphenyl-1-picrylhydrazyl. In addition, the catalytic activities of pillar[5]arene imidazole-1 and pillar[5]arene imidazole-2 by reduction of 4-nitrophenol were studied, indicating the catalytic reduction of 4-nitrophenol was 93.0 % for the pillar[5]arene imidazole-1 catalyst at 18 min. Comparison of the reactivity of pillar[5]arene imidazole-1 with that of pillar[5]arene imidazole-2 shows an increase in antibacterial and catalytic activity. This study summarized that using suitable catalysts, catalytic reduction aims to convert the most harmful and toxic organic compound 4-nitrophenol into non-toxic 4-aminophenol and popularize it in industry.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108544"},"PeriodicalIF":4.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892183","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 mining and characterization of bifunctional Clerodane Diterpene synthase from a fungus Myrothecium sp","authors":"Shuxuan Li ,&nbsp;Ke Ma ,&nbsp;Yujie Zhao ,&nbsp;Luning Zhou ,&nbsp;Peng Zhang ,&nbsp;Hanwei Liu ,&nbsp;Yajin Ye ,&nbsp;Wenhan Lin ,&nbsp;Jaclyn M. Winter ,&nbsp;Guangwei Wu","doi":"10.1016/j.bioorg.2025.108548","DOIUrl":"10.1016/j.bioorg.2025.108548","url":null,"abstract":"<div><div>Clerodane diterpenoids are a promising group of pharmacological molecules and are rarely discovered in fungi. The clerodane diterpene synthase has not yet been characterized in fungi. Herein, we discovered a gene, <em>mterA</em>, encoding chimeric protein with the bifunction of class II and class I synthases from a fungus <em>Myrothecium</em> sp. by genome mining. Heterologous co-expression of <em>mterA</em> and <em>mterB</em> in engineered yeast led to the production of a clerodane diterpene product (5<em>S</em>, 8<em>R</em>, 9<em>R</em>, 10<em>S</em>)-terpentetriene (<strong>1</strong>), confirming the existence of a fungi-derived special clerodane diterpene synthase. Site-directed mutagenesis on conserved motifs revealed a strong influence on terpentetriene accumulation. Gene inactivation of <em>mterA</em> indicated that the <em>mter</em> gene cluster was likely cryptic or weakly expressed in the host under the laboratory conditions. Compound <strong>1</strong> exhibited significant inhibitory activity against the plant pathogen <em>Bacillus subtilis</em> with a MIC value of 8 μg/mL and activated the plant immune response. MterA representes the first chimeric bifunctional clerodane diterpene synthase.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108548"},"PeriodicalIF":4.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892169","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":"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":"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":"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}

{"title":"Limonoids and semisynthetic derivatives as anticancer agents: Recent research progress and future perspectives","authors":"Qihui Wang ,&nbsp;Bingyu Kou ,&nbsp;Jingze Wang ,&nbsp;Haoming Song ,&nbsp;Jian Gao ,&nbsp;Yimeng Sun ,&nbsp;Lin Wang ,&nbsp;Xin Jin","doi":"10.1016/j.bioorg.2025.108520","DOIUrl":"10.1016/j.bioorg.2025.108520","url":null,"abstract":"","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108520"},"PeriodicalIF":4.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881388","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":"Deciphering the landscape of allosteric glutaminase 1 inhibitors as anticancer agents","authors":"Chiara Vagaggini ,&nbsp;Pasqualina D’Ursi ,&nbsp;Federica Poggialini ,&nbsp;Paola Fossa ,&nbsp;Valeria Francesconi ,&nbsp;Gabriele Trombetti ,&nbsp;Alessandro Orro ,&nbsp;Elena Dreassi ,&nbsp;Silvia Schenone ,&nbsp;Michele Tonelli ,&nbsp;Anna Carbone","doi":"10.1016/j.bioorg.2025.108523","DOIUrl":"10.1016/j.bioorg.2025.108523","url":null,"abstract":"<div><div>Glutamine is the second most utilised energy source after glucose for cancer cells to support their proliferation and survival. Glutaminase 1 (GLS1) is the rate-limiting enzyme during the glutaminolysis pathway and thus represents a promising therapeutic target for the development of innovative antitumor agents. Two main classes of GLS1 inhibitors, based on their different binding mode, are reported: the substrate active site and the allosteric site inhibitors. Despite the intense efforts made to date, only two GLS1 inhibitors (<em>i.e.,</em> <strong>CB-839</strong> and <strong>IPN60090</strong>) have entered clinical trials. Therefore, this research field remains to be explored to improve the effectiveness of anticancer therapy. Hence, we describe the discovery and development of reversible allosteric GLS1 inhibitors disclosed in the last six years, dividing them based on their structural similarity with bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (<strong>BPTES</strong>) and <strong>CB-839</strong>. Furthermore, macrocyclic and thiadiazole derivatives, and other structurally different compounds are discussed to present a wider picture of the chemical space under investigation. The study of the binding interactions governing GLS1 inhibition is also analyzed, to help prospectively refine the structural features for greater efficacy. Interestingly, an overview of a new class of irreversible allosteric inhibitors targeting GLS1 Lys320 key residue is provided for the first time. We also summarize the most important biological studies conducted on <strong>CB-839</strong> and <strong>IPN60090</strong> and their significance for further assessment. The insights garnered from this paper are expected to guide future drug design endeavours toward the identification of novel therapeutics targeting GLS1 to complement and potentially enhance the arsenal of anticancer medications.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108523"},"PeriodicalIF":4.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892185","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 chalcone candidates as potential in vitro and in vivo anti-inflammatory agents: Synthesis, in silico docking, multitarget bioevaluation and molecular dynamic simulation","authors":"Alshimaa Kh.M. Ahmed ,&nbsp;Eman A.M. Beshr ,&nbsp;Ibrahim M. Salem ,&nbsp;Osama A.A. Ahmed ,&nbsp;Tarek S. Ibrahim ,&nbsp;Deiaa E. Elsayed Abouzed ,&nbsp;Ahmed Mostafa Mahmoud ,&nbsp;Mamdouh F.A. Mohamed","doi":"10.1016/j.bioorg.2025.108540","DOIUrl":"10.1016/j.bioorg.2025.108540","url":null,"abstract":"<div><div>Managing inflammation with the commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) represents a critical challenge in modern medicine because of its strong influence on the cyclooxygenase-1 (COX-1) enzyme might induce substantial adverse effects. Therefore, there is urgent necessity for the exploration of safer alternatives, particularly cyclooxygenase-2 (COX-2) inhibitors. This study aimed to address this issue through the synthesis and evaluation of 19 new chalcone derivatives (<strong>2a-m</strong> and <strong>4a-f</strong>) for their <em>in vitro</em> anti-inflammatory activity against various biotargets including iNOS, COX-2, 5-LOX, PGE2, and TNFα. Moreover, these compounds showed moderate to strong anti-inflammatory activity in the carrageenan rat paw edema test. Compounds <strong>2a</strong>, <strong>2f</strong>, <strong>2</strong> <strong>h</strong>, <strong>2</strong> <strong>m</strong>, and <strong>4b</strong> are promising candidates for the treatment of inflammatory diseases. In particular, compound <strong>4b</strong> was demonstrated to be the most effective derivative as a nitric oxide release inhibitor, exhibiting a 61.7 % inhibition rate. It exhibited substantial selectivity for COX-2 (IC₅₀ = 1.933 μM) compared to COX-1 (IC₅₀ = 5.526 μM). Compound <strong>4b</strong> exhibited notable inhibitory activity against 5-LOX (IC₅₀ = 2.112 μM) and demonstrated considerable inhibitory activity against iNOS, PGE2, and TNF-α biotargets in LPS-stimulated RAW cells, with IC₅₀ values of 114.18, 37.13, and 58.15 nM, respectively. The <em>in vivo</em> anti-inflammatory effects demonstrated the significant efficacy of compound <strong>4b</strong>, as evidenced by a notable edema inhibition rate of 37.05 %, along with minimal ulcerogenic activity observed in the histopathological findings. <em>In silico</em> experiments demonstrated that the intermolecular contacts of the most active chemical <strong>4b</strong> with the biotargets COX-2, 5-LOX, and iNOS were analyzed by docking, revealing significant binding interactions. The stability of the interactions between compound <strong>4b</strong> and the targets COX-2, 5-LOX, and iNOS was assessed using a standard 100 ns atomistic dynamic simulation method. Various parameters derived from MD simulation trajectories were adjusted and validated to confirm the stability of the generated complexes under dynamic settings. Ultimately, compound <strong>4b</strong> exhibited favorable physicochemical properties and satisfactory drug-likeness, indicating its potential as an oral anti-inflammatory agent, warranting additional structure-activity relationship investigation and optimization.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"161 ","pages":"Article 108540"},"PeriodicalIF":4.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887212","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}