Bioorganic Chemistry最新文献_第8页

Chemical constituents from the mangrove-derived fungus Quambalaria cyanescens and their antibacterial activity. 红树源真菌金葵的化学成分及其抑菌活性。

IF 5.1 2区医学

Bioorganic Chemistry Pub Date : 2026-10-05 Epub Date: 2026-08-14 DOI: 10.1016/j.bioorg.2026.110382

Hong Xiao, Pei Lv, Xiaobo Liu, Jingyu Yang, Bin Gong, Tiantao Xiong, Jie Wang, Kun Wang, Wanshan Li, Yuyue Qin, Guangying Chen

{"title":"Chemical constituents from the mangrove-derived fungus Quambalaria cyanescens and their antibacterial activity.","authors":"Hong Xiao, Pei Lv, Xiaobo Liu, Jingyu Yang, Bin Gong, Tiantao Xiong, Jie Wang, Kun Wang, Wanshan Li, Yuyue Qin, Guangying Chen","doi":"10.1016/j.bioorg.2026.110382","DOIUrl":"10.1016/j.bioorg.2026.110382","url":null,"abstract":"Vibriosis poses a significant bacterial threat to aquaculture, affecting a diverse range of fish and shellfish. In this study, a novel dibenzo[b,f]oxepin analogue, phylloplaoxepin A (1), and four new 1,4-naphthoquinone analogues, phylloplaquinones A-D (2-5), along with two known compounds 6 and 7 were isolated from the mangrove-derived fungus Quambalaria cyanescens HLLP-241. Compounds 4 and 6 exhibited potent inhibition against V. alginolyticus, with both exhibiting a MIC values of 3.125 (chloramphenicol, MIC = 1.56 μg/mL). Compounds 3 and 5-7 exhibited significant inhibitory effects against V. parahaemolyticus, each with a MIC values of 0.78 μg/mL, comparable to the positive control (chloramphenicol, MIC = 0.78 μg/mL). Mechanistic studies reveal that compound 4 inhibits biofilm formation of V. alginolyticus in a dose-dependent manner, while simultaneously disrupting membrane integrity, depleting ATP, and inducing accumulation of reactive oxygen species (ROS). Transcriptomic analysis, qRT-PCR validation, molecular docking, molecular dynamics simulations, and enzymatic assays collectively demonstrate that SerA is the key functional target of compound 4 in inhibiting the growth of V. alginolyticus.","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110382"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786278","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}

引用次数: 0

Benzo[h]quinoline-based heterocyclic derivatives as Culex pipiens larvicidal candidates: synthesis, bioactivity, biochemical response, and in silico mechanistic insights. 基于苯并[h]喹啉的杂环衍生物作为杀幼库蚊的候选者：合成、生物活性、生化反应和硅机制的见解。

IF 5.1 2区医学

Bioorganic Chemistry Pub Date : 2026-10-05 Epub Date: 2026-08-17 DOI: 10.1016/j.bioorg.2026.110407

Eman A E El-Helw, Mahmoud Kamal, Eslam M Hosni, Amira A El-Sayed, Hany M Abd El-Lateef, Sayed K Ramadan

{"title":"Benzo[h]quinoline-based heterocyclic derivatives as Culex pipiens larvicidal candidates: synthesis, bioactivity, biochemical response, and in silico mechanistic insights.","authors":"Eman A E El-Helw, Mahmoud Kamal, Eslam M Hosni, Amira A El-Sayed, Hany M Abd El-Lateef, Sayed K Ramadan","doi":"10.1016/j.bioorg.2026.110407","DOIUrl":"10.1016/j.bioorg.2026.110407","url":null,"abstract":"A new series of benzo[h]quinoline-based heterocyclic derivatives was synthesized and evaluated as larvicidal candidates against third instar Culex pipiens larvae. The prepared compounds showed concentration-dependent toxicity with clear structure-related variation across the series. Benzo[h]quinolone-triazinone hybrid 3 was the most active derivative, giving the lowest LC50 value (142 ± 0.2 μg/mL) and the highest toxicity index (100), and was approximately 2.1-fold more potent than chlorpyrifos under the same assay conditions. Biochemical evaluation of triazinone 3 revealed significant reductions in acetylcholinesterase activity and in total protein, carbohydrate, and lipid contents compared with untreated larvae, indicating that larval mortality was accompanied by cholinergic disturbance and depletion of metabolic reserves. Molecular docking was performed for all synthesized compounds against acetylcholinesterase (AChE) and nicotinic acetylcholine receptor (nAChR), whereas molecular dynamics simulations were applied to the bioassay-selected compound 3 and the reference systems to examine the dynamic behavior of the predicted complexes. Triazinone 3 maintained a stable AChE complex during simulation and showed persistent contacts with residues including SER250, TRP212, HIS567, PHE416, THR252, TYR258, SER327, and PHE457. In the nAChR model, the trajectory was more mobile but retained recurrent contacts involving ASP153, ASN196, SER149, LYS198, TYR200, TYR152, LYS156, and TYR94. SwissADME analysis further suggested that the activity profile was influenced by a balance between target-recognition potential and physicochemical accessibility. Overall, the findings identify benzo[h]quinoline-based heterocycles, particularly triazinone 3, as promising larvicidal scaffolds and support further optimization of this class as potential alternatives to conventional insecticides.","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110407"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786326","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}

引用次数: 0

Repurposing butoconazole as a GRP78 substrate-binding domain (SBD) inhibitor to induce endoplasmic reticulum stress-mediated apoptosis in triple-negative breast cancer. 丁唑康唑作为GRP78底物结合域（SBD）抑制剂诱导三阴性乳腺癌内质网应激介导的细胞凋亡

IF 5.1 2区医学

Bioorganic Chemistry Pub Date : 2026-10-05 Epub Date: 2026-08-27 DOI: 10.1016/j.bioorg.2026.110447

Yaowen Song, Ziyue Yuan, Zhijia Li, Yunli Huang, Yingying Lu, Qianqian Yang, Yan Wang, Lan Zhang, Wei Ma

{"title":"Repurposing butoconazole as a GRP78 substrate-binding domain (SBD) inhibitor to induce endoplasmic reticulum stress-mediated apoptosis in triple-negative breast cancer.","authors":"Yaowen Song, Ziyue Yuan, Zhijia Li, Yunli Huang, Yingying Lu, Qianqian Yang, Yan Wang, Lan Zhang, Wei Ma","doi":"10.1016/j.bioorg.2026.110447","DOIUrl":"10.1016/j.bioorg.2026.110447","url":null,"abstract":"Triple-negative breast cancer (TNBC) is aggressive with limited therapies and poor prognosis. Butoconazole, a clinical topical imidazole antifungal for vulvovaginal candidiasis, has not previously been investigated for TNBC treatment. Here, we repurposed butoconazole as a novel allosteric inhibitor of glucose-regulated protein 78 (GRP78) for TNBC treatment. It suppressed TNBC cell proliferation (IC50: 13.61 ± 1.07 μM for MDA-MB-231, 26.17 ± 1.17 μM for MDA-MB-468), inhibited migration, and induced apoptosis, resulting in 68.28% tumor growth inhibition in MDA-MB-231 xenograft mouse models without evident toxicity. Mechanistically, we combined RNA-seq and limited proteolysis-mass spectrometry (LiP-MS) to identify GRP78 as its potential target, validated by surface plasmon resonance (SPR), biolayer interferometry (BLI), cellular thermal shift assay (CETSA), drug-affinity-responsive target-stability (DARTS) assay and molecular dynamics simulations. Unlike existing GRP78 modulators, butoconazole allosterically attaches to the helical bundle at the distal tip of GRP78 substrate-binding domain α (SBD-α), rearranges its binding pocket and blocks GRP78 chaperone activity. This triggers endoplasmic reticulum (ER) stress, elevates the expression levels of ATF4 and CHOP and induces apoptosis. Rescue assays with 4-phenylbutyrate (4-PBA), ATF4/CHOP knockdown or GRP78 overexpression attenuated butoconazole's anti-tumor activity. Collectively, butoconazole suppresses TNBC through allosteric GRP78 inhibition to trigger ER stress-mediated ATF4/CHOP apoptosis, and represents a promising lead compound for further development as a systemic anti-TNBC agent through formulation optimization.","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110447"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860274","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}

引用次数: 0

Benzylisoquinoline Alkaloids from NelumbinisPlumula as Potential Butyrylcholinesterase Inhibitors: Isolation, Characterization and Bioactivity Evaluation. 作为潜在丁酰胆碱酯酶抑制剂的莲属植物苯基异喹啉生物碱：分离、表征及生物活性评价

IF 5.1 2区医学

Bioorganic Chemistry Pub Date : 2026-10-05 Epub Date: 2026-08-31 DOI: 10.1016/j.bioorg.2026.110451

Wenjun Wei, Dongge Wang, Jigao Yang, Jinhao Yuan, Li Xu, Suxiang Feng

{"title":"Benzylisoquinoline Alkaloids from NelumbinisPlumula as Potential Butyrylcholinesterase Inhibitors: Isolation, Characterization and Bioactivity Evaluation.","authors":"Wenjun Wei, Dongge Wang, Jigao Yang, Jinhao Yuan, Li Xu, Suxiang Feng","doi":"10.1016/j.bioorg.2026.110451","DOIUrl":"10.1016/j.bioorg.2026.110451","url":null,"abstract":"Nelumbinis Plumula is a well-known traditional herb with medicinal and edible homology, which is commonly consumed as tea to clear heart-fire, calm the mind and improve sleep in daily life. A systematic phytochemical investigation on the extract of Nelumbinis Plumula was carried out, leading to the isolation of ten new benzylisoquinoline alkaloids (1-8, 17, and 18) and 14 known analogues (9-16, and 19-24). Their structures and absolute configurations were unambiguously established by comprehensive spectroscopic analysis and optical rotation measurements. Biological evaluation revealed that bisbenzylisoquinoline alkaloids 17, 18, 21, 22, and 23 possessed remarkable inhibitory effects against BChE, with IC50 values ranging from 1.52 to 6.51 μM. Further mechanistic investigations revealed that the new compounds 17 and 18 inhibited BChE via a mixed-type inhibitory mechanism. Moreover, molecular dynamics simulation, MM/GBSA binding energy calculation, and surface plasmon resonance assay verified that compound 18 exhibited superior inhibitory activity against BChE compared with compound 17, which was in good agreement with the results of in vitro enzymatic activity assay. These bisbenzylisoquinoline alkaloids can serve as BChE inhibitors, providing a theoretical basis for the application of Nelumbinis Plumula in the prevention of neurodegenerative diseases.","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110451"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863229","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}

引用次数: 0

Molecular insights into the antineoplastic mechanisms of mono- and bimetallic ruthenium(II) arene diamine complexes: a comprehensive evaluation. 单金属和双金属钌（II）芳烃二胺配合物抗肿瘤机制的分子洞察：综合评价。

IF 5.1 2区医学

Bioorganic Chemistry Pub Date : 2026-10-05 Epub Date: 2026-08-22 DOI: 10.1016/j.bioorg.2026.110430

Serdar Batıkan Kavukcu, Hafize Seda Vatansever, Feyzan Özdal-Kurt, Mehmet Korkmaz, Burcu Erbaykent, Hilal Kabadayı Ensarioğlu, Hayati Türkmen

{"title":"Molecular insights into the antineoplastic mechanisms of mono- and bimetallic ruthenium(II) arene diamine complexes: a comprehensive evaluation.","authors":"Serdar Batıkan Kavukcu, Hafize Seda Vatansever, Feyzan Özdal-Kurt, Mehmet Korkmaz, Burcu Erbaykent, Hilal Kabadayı Ensarioğlu, Hayati Türkmen","doi":"10.1016/j.bioorg.2026.110430","DOIUrl":"10.1016/j.bioorg.2026.110430","url":null,"abstract":"Although platinum-based therapies are of central importance in oncology, their clinical benefits are often limited by systemic toxicity and the emergence of drug resistance. This study, a mechanistic continuation of our previous research on the cytotoxicity of organometallic Ru(II) complexes, presents a comprehensive in vitro investigation of the antineoplastic pathways of monometallic (Ru1) and bimetallic Ru(II) arene complexes (Ru2, Ru3) carrying diamine ligands. We evaluated their efficacy in prostate (PC-3, DU145) and colorectal (HT-29) cancer models, as well as in non-cancerous Vero cells. Morphological assessments and long-term wound healing tests revealed that the bimetallic complex (Ru3) significantly suppressed cellular motility and caused total cell death over a 7-day period. Immunocytochemical analysis of γ-H2AX foci confirmed that the complexes caused potent DNA double-strand breaks, and Ru3 demonstrated superior genotoxic activity in all cell lines. Mechanistic elucidation via flow cytometry and immunoblotting revealed that these complexes trigger a p53-dependent mitochondrial apoptotic pathway characterized by depolarization of the mitochondrial membrane potential, significant release of Cytochrome C, followed by Caspase-3 and PARP activation. Furthermore, treatment caused a remarkable reduction in anti-apoptotic Bcl-2 and Bcl-xL proteins. In particular, Ru1 exhibited unique antioxidant-like properties by reducing intracellular ROS and 8-OHdG levels in specific cell lines, suggesting a novel protective role in oxidative metabolism as well as its anticarcinogenic potential. Collectively, these results provide a potent molecular map for the activity of these Ru(II) diamine complexes and highlight Ru3 as a strong candidate for the development of next-generation, targeted anticancer therapies.","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110430"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148816983","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}

引用次数: 0

Discovery of a novel CDK8 inhibitor as dual suppressor of NF-κB-driven inflammation and promoter of Treg differentiation for psoriasis treatment. 发现一种新的CDK8抑制剂作为NF-κ b驱动炎症的双重抑制因子和Treg分化的促进因子治疗银屑病。

IF 5.1 2区医学

Bioorganic Chemistry Pub Date : 2026-10-05 Epub Date: 2026-08-27 DOI: 10.1016/j.bioorg.2026.110419

Cencen Lei, Dalong Jin, Ajun Liu, Yumeng Wang, Xingxing Zhang, Xinhua Liu

{"title":"Discovery of a novel CDK8 inhibitor as dual suppressor of NF-κB-driven inflammation and promoter of Treg differentiation for psoriasis treatment.","authors":"Cencen Lei, Dalong Jin, Ajun Liu, Yumeng Wang, Xingxing Zhang, Xinhua Liu","doi":"10.1016/j.bioorg.2026.110419","DOIUrl":"10.1016/j.bioorg.2026.110419","url":null,"abstract":"Cyclin-dependent kinase 8 (CDK8) has emerged as an important regulator of inflammatory signaling and immune homeostasis, representing a promising therapeutic target for psoriasis and other immune-mediated diseases. Herein, we report the structure-based optimization of the previously reported CDK8 inhibitor to develop a series of novel derivatives. Through systematic structure-activity relationship (SAR) analysis, compound LW-1 was identified as a lead candidate with potent CDK8 inhibitory activity (IC50 = 24.5 ± 1.4 nM) and significantly improved metabolic stability. Target engagment studies confirmed that LW-1 directly binds to CDK8 with high affinity. Mechanistically, LW-1 suppressed NF-κB-dependent transcription and reduced pro-inflammatory cytokine expression, while promoting regulatory T cell (Treg) differentiation through modulation of the STAT1 and TGF-β/Smad signaling pathways. Pharmacokinetic evaluation revealed that LW-1 possessed markedly improved metabolic stability (t₁/₂ = 37.11 min in mouse liver microsome) and prolonged elimination half-life in rats (t₁/₂ = 4.8 h, po), along with acceptable oral bioavailability (F = 27.1%). In the IMQ-induced psoriasis-like mouse model, LW-1 markedly alleviated skin inflammation by promoting Treg differentiation and suppressing pro-inflammatory cytokine production. Collectively, LW-1 represents a promising CDK8 inhibitor with improved drug-like properties and potent anti-psoriatic efficacy, providing a potential therapeutic candidate for the treatment of psoriasis and other inflammatory diseases.","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110419"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849510","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}

引用次数: 0

Discovery and mechanistic benchmarking of ACE inhibitory Di- and tripeptides. ACE抑制二肽和三肽的发现和机制基准。

IF 5.1 2区医学

Bioorganic Chemistry Pub Date : 2026-10-05 Epub Date: 2026-08-29 DOI: 10.1016/j.bioorg.2026.110452

Yi Li, Yongqiang Cheng, Ning Tang

{"title":"Discovery and mechanistic benchmarking of ACE inhibitory Di- and tripeptides.","authors":"Yi Li, Yongqiang Cheng, Ning Tang","doi":"10.1016/j.bioorg.2026.110452","DOIUrl":"10.1016/j.bioorg.2026.110452","url":null,"abstract":"Synthetic angiotensin-converting enzyme (ACE) inhibitors demonstrate clinical efficacy, but their adverse effects stimulate interest in natural, food-derived alternatives. We employed an integrated computational framework to systematically screen all possible di- and tripeptides for ACE inhibitory potential, followed by in vitro experimental validation. Computational screening, benchmarked against clinical drugs, revealed that aromatic residues, particularly tryptophan (W), phenylalanine (F), and tyrosine (Y), dominate high-affinity sequences, with binding primarily driven by van der Waals and hydrophobic interactions. Structural analysis demonstrated that the N-terminal WW motif is critical for optimal binding. DFT calculations showed that high-affinity peptides possessed narrow HOMO-LUMO gaps (4.72-4.96 eV), high polarizability (> 500 a.u.), and low chemical hardness. Experimental dose-response assays of the top-ranked candidates validated the computational pipeline, demonstrating a strong rank-order agreement between predicted binding affinities and measured inhibitory potency. Notably, the tryptophan-rich peptides WW, WWY, and WWF exhibited IC50 values of 0.108, 0.134, and 0.136 mM, respectively, underscoring the dominant role of tryptophan in ACE inhibition. These findings establish a validated computational framework and actionable design principles for peptide-based drug discovery, highlighting tryptophan-rich peptides as promising lead molecules of ACE inhibitory candidates for further investigation.","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110452"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148856858","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}

引用次数: 0

Selective anticancer activity of a multinuclear Cu(II) complex through apoptosis induction in ovarian cancer cells. 多核Cu（II）复合物通过诱导卵巢癌细胞凋亡的选择性抗癌活性。

IF 5.1 2区医学

Bioorganic Chemistry Pub Date : 2026-10-05 Epub Date: 2026-08-16 DOI: 10.1016/j.bioorg.2026.110383

Li Gong, Mostafa Heidari Majd, Hamid Reza Ghaffari

{"title":"Selective anticancer activity of a multinuclear Cu(II) complex through apoptosis induction in ovarian cancer cells.","authors":"Li Gong, Mostafa Heidari Majd, Hamid Reza Ghaffari","doi":"10.1016/j.bioorg.2026.110383","DOIUrl":"10.1016/j.bioorg.2026.110383","url":null,"abstract":"Copper Cu(II)-based coordination compounds have attracted considerable attention as potential alternatives to platinum-based anticancer agents because of their diverse mechanisms of action and improved selectivity. In this study, a multinuclear Cu(II) complex, [Cu(DMPN)2(H2O)][Cu2(μ-DPA)4Cu(DMPN)2].H2O (Cu-DPA-DMPN), was investigated for its anticancer activity against human ovarian carcinoma (OVCAR-3) cells. The complex was characterized by FTIR spectroscopy and ESI-MS, confirming successful coordination of DPA and DMPN ligands to the Cu(II) centers. Cytotoxicity assays demonstrated dose- and time-dependent antiproliferative activity, with IC50 values of 73.06 μM and 35.75 μM after 48 and 72 h, respectively, while exhibiting lower toxicity toward non-malignant CHO cells (IC50 = 334.19 μM at 48 h). Flow cytometry revealed a significantly higher percentage of early apoptotic cells following Cu-DPA-DMPN treatment than with cisplatin. Gene expression analysis showed marked upregulation of Caspase-3 (160.9-fold) and suppression of AKT1 (0.12-fold), indicating activation of apoptotic signaling and inhibition of cell survival pathways. JC-1 analysis further demonstrated mitochondrial membrane depolarization, supporting the functional involvement of mitochondria during apoptosis. In addition, the complex did not significantly increase TLR6 expression in CHO cells, suggesting minimal inflammatory effects on normal cells. These findings demonstrate that the Cu-DPA-DMPN complex exhibits selective anticancer activity by promoting apoptosis while displaying reduced toxicity toward normal cells, highlighting its potential as a promising candidate for ovarian cancer therapy.","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110383"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823477","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}

引用次数: 0

Recent progress in cancer detection and therapeutic applications of calixarene- and pillararene-based systems. 杯芳烃和柱芳烃系统在癌症检测和治疗中的应用进展。

IF 5.1 2区医学

Bioorganic Chemistry Pub Date : 2026-10-05 Epub Date: 2026-07-07 DOI: 10.1016/j.bioorg.2026.110226

Paula M Marcos, Peter J Cragg

{"title":"Recent progress in cancer detection and therapeutic applications of calixarene- and pillararene-based systems.","authors":"Paula M Marcos, Peter J Cragg","doi":"10.1016/j.bioorg.2026.110226","DOIUrl":"10.1016/j.bioorg.2026.110226","url":null,"abstract":"Macrocycles, such as calixarenes and pillararenes, have received more focus as potential therapeutic agents and drug carriers. They can solubilize/encapsulate different anti-cancer drugs by host-guest interactions or self-assembly. Good chemical stability, good compatibility, responsiveness to external stimuli and low toxicity to normal cells are properties that make these macrocycles good candidates for cancer detection and therapy. This review focuses on strategies developed for cancer detection and therapeutics by calixarenes and pillararenes over the past decade (from 2015 to 2025). Cone calix[4]arene platform has been the most widely investigated, but examples of calix[5,6,8]arenes have also been reported. Pillar[n]arenes, like calixarenes, exist in a range of homologues up to pillar[10]arene, however, pillar[5]arenes and pillar[6]arenes have cavity sizes most suited to drug encapsulation. Developments and applications in biosensing, bioimaging, drug delivery systems and cancer therapy are presented based on these macrocycles. Finally, conclusions and future perspectives of these macrocyclic compounds with anti-cancer activity are also provided.","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110226"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700316","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}

引用次数: 0

Exploring ULK family in human cancer: insights into mechanisms and therapeutic potential. 探索人类癌症中的ULK家族：对机制和治疗潜力的见解。

IF 5.1 2区医学

Bioorganic Chemistry Pub Date : 2026-10-05 Epub Date: 2026-08-13 DOI: 10.1016/j.bioorg.2026.110352

Mengjia Li, Mengqi Zhang, Chenlin Wen, Haitao Cheng, Xintong Li, Yangyang Han

{"title":"Exploring ULK family in human cancer: insights into mechanisms and therapeutic potential.","authors":"Mengjia Li, Mengqi Zhang, Chenlin Wen, Haitao Cheng, Xintong Li, Yangyang Han","doi":"10.1016/j.bioorg.2026.110352","DOIUrl":"10.1016/j.bioorg.2026.110352","url":null,"abstract":"The ULK (Unc-51-like kinase) family, a group of serine/threonine protein kinases, plays a central regulatory role in the initiation of autophagy. Autophagy has a dual role in cancer, as it can both inhibit tumor formation and promote the survival and progression of established tumors, making targeting autophagy an attractive therapeutic strategy for cancer. This review systematically explores the expression, function, and molecular mechanisms of the ULK family (including ULK1, ULK2, ULK3, ULK4, and SKT6) in various human cancers. Studies have shown that ULK family members play complex and sometimes contradictory roles in different cancer types and histological backgrounds, functioning as both tumor suppressors and oncogenes. Their functions are precisely regulated through multiple signaling pathways, such as mTOR and AMPK, and influence key cancer characteristics, including cell survival, proliferation, metabolic adaptation, metastasis, and drug resistance. Additionally, this review focuses on the latest progress in targeting the ULK family (particularly the development of selective ULK small molecule inhibitors) and their therapeutic potential as monotherapies or in combination with chemotherapy, targeted therapy, and immunotherapy. Despite challenges, such as understanding their context-dependent functions and refining biomarkers, targeting the ULK family, which represents the initiation step of autophagy, opens up a promising path for the development of novel anti-cancer therapies.","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110352"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757249","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}

引用次数: 0