Bioorganic & Medicinal Chemistry最新文献_第8页

Exogenous/endogenous stimuli-responsive antitumor prodrugs advance precision chemotherapy 外源性/内源性刺激应答性抗肿瘤前药推进精准化疗。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry

Pub Date : 2025-11-14 DOI: 10.1016/j.bmc.2025.118485

Luo Wang , Jingao Li , Xuanwei Zeng , Qinyue Lu , Yifeng Wang , Zulhumar Anwar , Li Xue , Heli Fan , Huabing Sun

Precision chemotherapy aims to selectively target cancer cells while sparing healthy cells, thereby addressing a major challenge in traditional chemotherapy, off-target toxicity. Stimuli-responsive antitumor prodrugs leverage exogenous or endogenous triggers for targeted drug activation, which represents a significant advancement in this field. Exogenous stimuli, such as light, ionizing radiation, and ultrasound, usually offer spatiotemporal precision at tumor sites to minimize systemic side effects. Similarly, endogenous stimuli, including hypoxia, acidic pH, the overexpression of specific enzymes, and elevated levels of reactive oxygen species (ROS) and glutathione (GSH), exploit the unique tumor microenvironment to facilitate selective activation. These prodrugs undergo specific chemical or enzymatic reactions in response to their respective triggers, releasing active therapeutic agents at desired sites. This review provides an overall analysis of recent advances in both exogenous and endogenous stimuli-responsive prodrugs, with a focus on their design principles, activation mechanisms, and therapeutic efficacy. By highlighting these emerging strategies, we aim to underscore the potential of stimuli-responsive prodrugs to enhance therapeutic efficacy and safety, paving the way for precision chemotherapy.

精确化疗旨在选择性地靶向癌细胞，同时保留健康细胞，从而解决传统化疗的主要挑战，脱靶毒性。刺激反应性抗肿瘤前药利用外源性或内源性触发器进行靶向药物激活，这代表了该领域的重大进展。外源性刺激，如光、电离辐射和超声，通常提供肿瘤部位的时空精度，以尽量减少全身副作用。同样，内源性刺激，包括缺氧、酸性pH、特定酶的过度表达、活性氧（ROS）和谷胱甘肽（GSH）水平升高，利用独特的肿瘤微环境促进选择性激活。这些前药经过特定的化学或酶反应，以响应各自的触发因素，在所需的部位释放活性治疗剂。本文综述了外源性和内源性刺激反应性前药的最新进展，重点介绍了它们的设计原理、激活机制和治疗效果。通过强调这些新兴策略，我们旨在强调刺激反应性前药在提高治疗疗效和安全性方面的潜力，为精确化疗铺平道路。

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引用次数: 0

Peptide-based antibiotics: structure-driven strategies to tackle toxicity and resistance of antimicrobial peptides 基于多肽的抗生素：结构驱动的策略来解决抗菌肽的毒性和耐药性

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry

Pub Date : 2025-11-12 DOI: 10.1016/j.bmc.2025.118486

Maryam Tabarzad , Maryam Torshabi , Azadeh Haeri , Fariba Fathi , Seyedeh Maryam Mortazavi

Antimicrobial peptides (AMPs) are a prominent weapon that can expand human beings' arsenal against antimicrobial resistance. However, microorganisms can equip themselves against the antimicrobial effects of AMPs. Increasing daily dosing of AMPs to dispel resistance may lead to severe side effects or toxicity. In addition, some poor properties of AMPs, such as rapid degradation and low water solubility, make it difficult to achieve the right therapeutic dose at the target site. To provide more potent and less toxic AMPs, structural modification is one of the promising approaches. This review focuses on five representative AMPs: daptomycin, pexiganan (MSI-78), murepavadin (POL7080), iseganan (IB-367), and omiganan (MBI-226), and involves an analysis of their clinical development, mechanisms of resistance, toxicity profiles, and resultant outcomes. By investigating these specific cases, we derive critical insights into the factors influencing the emergence of resistance, the challenges posed by toxicity, and the structural limitations that have impeded the translation of AMPs into clinical applications. Furthermore, we discuss prospective peptide design strategies that may effectively address these challenges. Notably, we underscore the potential of structure-based strategies, including amino acid substitutions and conjugation with diverse molecular entities (such as small functional groups, synthetic polymers, peptides, and antibiotics), as promising pathways to mitigate these barriers and advance the development of clinically viable AMP therapeutics.

抗菌肽（AMPs）是一种重要的武器，可以扩大人类的武器库对抗抗菌素耐药性。然而，微生物可以装备自己对抗抗菌肽的抗菌作用。增加每日剂量的抗菌肽消除耐药性可能导致严重的副作用或毒性。此外，amp的一些较差的特性，如快速降解和低水溶性，使其难以在目标部位达到合适的治疗剂量。为了提供更有效和更低毒性的amp，结构修饰是一种很有前途的方法。本文综述了五种具有代表性的抗菌药物：达托霉素、培昔甘南（MSI-78）、穆里帕瓦丁（POL7080）、伊塞甘南（IB-367）和奥米甘南（MBI-226），并分析了它们的临床发展、耐药机制、毒性特征和结果。通过调查这些具体病例，我们对影响耐药性出现的因素、毒性带来的挑战以及阻碍抗菌肽转化为临床应用的结构限制有了重要的见解。此外，我们讨论了可能有效解决这些挑战的前瞻性肽设计策略。值得注意的是，我们强调了基于结构的策略的潜力，包括氨基酸取代和与不同分子实体（如小官能团、合成聚合物、肽和抗生素）的偶联，作为缓解这些障碍和推进临床可行的AMP治疗方法发展的有希望的途径。

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引用次数: 0

Triazole-based STING inhibitors 三唑类STING抑制剂

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry

Pub Date : 2025-11-08 DOI: 10.1016/j.bmc.2025.118484

Anju Singh , Leonard Barasa , Leo DeOrsey , Maeve D. O'Reilly , Shruti Choudhary , Sara E. Cahill , Thomas Rossetti , Robert Madison Green , Fiachra Humphries , Paul R. Thompson

Aberrant activation of the DNA sensing cGAS–STING pathway has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), systemic lupus erythematosus (SLE), and autoinflammatory disorders such as Aicardi-Goutières syndrome (AGS) and STING-associated vasculopathy with onset in infancy (SAVI). Consequently, considerable efforts have been directed toward the development of STING inhibitors. We previously reported that BB-Cl-amidine and LB244 inhibit STING-dependent signalling with nanomolar potency both in vitro and in vivo. The nitrofuran warhead on LB244 provided superior potency and proteome-wide selectivity. Moreover, LB244 mirrored the efficacy of BB-Cl-amidine in vivo. Herein, we describe the development of a series of triazole-based analogues designed to inhibit STING signalling. These efforts led to the development of ASF24, a highly potent inhibitor of STING signalling (IC₅₀ = 0.49 μM). In summary, our findings identify a novel triazole-based STING inhibitor and establish a promising scaffold for the development of therapeutics targeting STING-mediated inflammatory diseases.

DNA感应cGAS-STING通路的异常激活与肌萎缩性侧索硬化症（ALS）、系统性红斑狼疮（SLE）和自身炎症性疾病（如aicardii - gouti综合征（AGS）和婴儿期发作的sting相关血管病变（SAVI））的发病机制有关。因此，相当多的努力已经指向开发STING抑制剂。我们之前报道过BB-Cl-amidine和LB244在体外和体内以纳米摩尔的效力抑制sting依赖的信号传导。硝基呋喃战斗部在LB244上具有优越的效力和蛋白质组选择性。此外，LB244在体内反映了bb - cl -脒的功效。在这里，我们描述了一系列基于三唑的类似物的发展，旨在抑制STING信号传导。这些努力导致了ASF24的开发，ASF24是一种高效的STING信号抑制剂（IC50 = 0.49 μM）。总之，我们的研究发现了一种新的基于三唑的STING抑制剂，并为开发针对STING介导的炎症性疾病的治疗方法建立了一个有希望的支架。

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引用次数: 0

Anti-NSCLC efficacy of a novel ROR1/PI3Kα/BRD4 multi-target inhibitor 一种新型ROR1/PI3Kα/BRD4多靶点抑制剂的抗nsclc疗效

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry

Pub Date : 2025-11-08 DOI: 10.1016/j.bmc.2025.118483

Ting Zhong , Ji Yun Lee , Qing Li , Fang Luo , Liang Xiong , Rongtao Wang , Jie Liu , Mingzhi Su , Lei Tang , Sang Kook Lee , Yanhua Fan

Receptor tyrosine kinase-like orphan receptor 1 (ROR1), phosphatidylinositol 3-kinase alpha (PI3Kα) and bromodomain-containing protein 4 (BRD4) are key therapeutic targets in non-small cell lung cancer (NSCLC), playing critical roles in tumourigenesis and disease progression. Despite this, no multi-targeted inhibitors that simultaneously target these three targets have been reported to date. Gefitinib improves survival in many NSCLC patients. However, its clinical utility is limited by drug resistance and adverse effects. We further discovered compound BIQO-9, which exhibits superior antitumor activity, based on a structure-activity relationship study of compound 9a. MTT assays demonstrated that BIQO-9 exhibited potent activity against A549 and H1975 cells, with IC₅₀ values of 0.49 μM and 0.22 μM, respectively—significantly lower than those of compound 9a (0.83 μM and 1.02 μM). Kinase activity assays further revealed enhanced inhibition of PI3Kα by BIQO-9 (IC₅₀ = 4.59 nM) compared to compound 9a (IC₅₀ = 13.12 nM). Additionally, Kinase profiling, biotin pull-down and cellular thermal shift assay (CETSA) identified BRD4 and ROR1 as additional direct targets of BIQO-9. Flow Cytometry analysis showed that BIQO-9 induces G₂ phase cell cycle arrest and promotes apoptosis in A549 cells. Western Blot analysis confirmed that its anti-NSCLC effect was achieved by simultaneously inhibiting the downstream signaling pathways of ROR1, PI3K and BRD4. Notably, BIQO-9 could significantly enhance the efficacy of Gefitinib in inducing cell apoptosis and G₂ phase arrest. This synergistic effect has also been verified in mouse xenograft model. To our knowledge, BIQO-9 represents the first ROR1/PI3Kα/BRD4 multi-target inhibitor with therapeutic potential in NSCLC. Moreover, the combination of BIQO-9 and Gefitinib offers a promising novel strategy for NSCLC treatment.

受体酪氨酸激酶样孤儿受体1 （ROR1）、磷脂酰肌醇3-激酶α (PI3Kα)和含溴结构域蛋白4 （BRD4）是非小细胞肺癌（NSCLC）的关键治疗靶点，在肿瘤发生和疾病进展中起关键作用。尽管如此，迄今为止还没有报道同时靶向这三个靶点的多靶点抑制剂。吉非替尼提高了许多非小细胞肺癌患者的生存率。然而，其临床应用受到耐药性和不良反应的限制。通过对化合物9a的构效关系研究，我们进一步发现了具有较强抗肿瘤活性的化合物BIQO-9。MTT实验表明，BIQO-9对A549和H1975细胞具有较强的活性，IC50值分别为0.49 μM和0.22 μM，显著低于化合物9a （0.83 μM和1.02 μM）。激酶活性测定进一步显示，BIQO-9对PI3Kα的抑制作用（IC50 = 4.59 nM）比化合物9a （IC50 = 13.12 nM）增强。此外，激酶谱分析、生物素下拉和细胞热移测定（CETSA）发现BRD4和ROR1是BIQO-9的额外直接靶点。流式细胞术分析显示BIQO-9诱导A549细胞G₂期细胞周期阻滞，促进细胞凋亡。Western Blot分析证实其抗nsclc作用是通过同时抑制ROR1、PI3K和BRD4下游信号通路实现的。值得注意的是，BIQO-9能显著增强吉非替尼诱导细胞凋亡和G2期阻滞的效果。这种协同效应在小鼠异种移植物模型中也得到了证实。据我们所知，BIQO-9是首个在非小细胞肺癌中具有治疗潜力的ROR1/PI3Kα/BRD4多靶点抑制剂。此外，BIQO-9联合吉非替尼为非小细胞肺癌治疗提供了一种有前景的新策略。

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引用次数: 0

Pyranotacrines as prospective multi-target compounds against Alzheimer's disease 吡诺他林作为治疗阿尔茨海默病的前瞻性多靶点化合物。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry

Pub Date : 2025-11-07 DOI: 10.1016/j.bmc.2025.118480

Salma Fares, Walaa M. El Husseiny, Khalid B. Selim, Mohammed A.M. Massoud

A series of tacrine-based 4-H-pyran derivatives were synthesized and biologically estimated as multifactorial ligands against Alzheimer's disease. Pyranotacrines were characterized by having the main core tacrine (ChE inhibition) and tetrahydro-4H-pyran (calcium channel blockers and β-amyloid activity). Among the series, compound 6c displayed a well-balanced multi-targeted activity against Alzheimer's disease and it was a potent AChE inhibitor with IC₅₀ = 0.06 ± 0.005 μM, approximately 3-folds more active than tacrine as a reference drug. Kinetic analysis and molecular docking displayed that 6c targeted both key binding regions of AChE. Moreover, its inhibitory activity against BuChE was 8-folds more active than rivastigmine with IC₅₀ = 0.09 ± 0.016 μM. Compound 6c showed blockade power of 46 % as a Ca²⁺ blockade agent and strong inhibition activity against β-amyloid with IC₅₀ = 1.09 ± 0.05 μM (71 % aggregation inhibition). Additionally, it showed higher anti-oxidative activity with 10.36 TE and chelating anchors activity for metal ions. The safety of 6c towards SH-SY5Y normal cells and HepG2 cancer cells was interesting with safety index ratio (Si = 2273), in addition to its BBB permeability and pharmacokinetic profile.

合成了一系列以他克林为基础的4- h -吡喃衍生物，并对其作为抗阿尔茨海默病的多因子配体进行了生物学评价。pyranopyrines的特点是具有主要核心的tacrine （ChE抑制）和四氢- 4h -pyran（钙通道阻滞剂和β-淀粉样蛋白活性）。其中，化合物6c对阿尔茨海默病表现出均衡的多靶点活性，是一种有效的AChE抑制剂，IC50 = 0.06±0.005 μM，比参比药物他克林活性高约3倍。动力学分析和分子对接表明，6c靶向了AChE的两个关键结合区。其对BuChE的抑制活性是利瓦斯汀的8倍，IC50 = 0.09±0.016 μM。化合物6c对β-淀粉样蛋白具有较强的抑制活性，IC50 = 1.09±0.05 μM（聚集抑制率71%）。此外，其抗氧化活性为10.36，对金属离子具有螯合锚定活性。6c对SH-SY5Y正常细胞和HepG2癌细胞的安全性值得关注，除了其血脑屏障通透性和药代动力学特征外，安全指数比（Si = 2273）。

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引用次数: 0

Design, synthesis, and biological evaluation of novel amino acid-Osimertinib conjugates as potential EGFR inhibitors 新型氨基酸-奥西替尼偶联物作为潜在EGFR抑制剂的设计、合成和生物学评价。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry

Pub Date : 2025-11-07 DOI: 10.1016/j.bmc.2025.118482

Hong-Ning Men , Peng-Fei Gu , Zheng Li , Yue Yu , Lin An , Ling Zhang , Tong-Hui Huang , You-Guang Zheng

In this study, a series of novel amino acid-conjugated Osimertinib scaffold derivatives were designed and synthesized as EGFR (T790M/L858R) mutations inhibitors. Notably, compound 10a potently inhibited EGFR (IC₅₀ = 0.046 μM) and displayed anti-proliferative activities against mutant non-small cell lung cancer cells (H1975 IC₅₀: 1.619 μM). Furthermore, compound 10a down-regulated the phosphorylation of EGFR, ERK and AKT in a dose-dependent manner in H1975 cells. At 5 μM, 10a suppressed p-ERK and p-AKT levels to 38 % and 40 % of control in H1975 cells, respectively. Cell cycle analysis revealed that compound 10a inhibited the proliferation of cells by inducing cell cycle arrest in the G1 phase. Molecular modeling indicated that compound 10a exhibited a binding mode analogous to that of Osimertinib. Overall, these results demonstrate the potential of 10a as an anticancer agent warranting further development.

本研究设计并合成了一系列新型氨基酸偶联奥西替尼支架衍生物，作为EGFR （T790M/L858R）突变抑制剂。值得注意的是，化合物10a对EGFR有抑制作用（IC50 = 0.046 μM），对突变型非小细胞肺癌细胞有抑制增殖作用（H1975 IC50: 1.619 μM）。此外，化合物10a在H1975细胞中以剂量依赖的方式下调EGFR、ERK和AKT的磷酸化。在5 μM下，10a抑制H1975细胞中p-ERK和p-AKT水平分别为对照组的38%和40%。细胞周期分析显示，化合物10a通过诱导细胞周期阻滞在G1期来抑制细胞增殖。分子模拟表明，化合物10a具有与奥西替尼类似的结合模式。总的来说，这些结果表明10a作为抗癌药物的潜力值得进一步开发。

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引用次数: 0

The role of P2Y1R in cardiovascular diseases and recent development of P2Y1R antagonists P2Y1R在心血管疾病中的作用及P2Y1R拮抗剂的最新进展。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry

Pub Date : 2025-11-07 DOI: 10.1016/j.bmc.2025.118479

Xiaozhen Liu , Shiyu Ma , Yongfang Yao , Yongtao Duan , Ruijun Li , Chuanjun Song

Cardiovascular diseases (CVDs) impose an enormous social burden. Given that cardiovascular diseases are accompanied by multiple complications and traditional treatment methods fail to provide a complete cure, there is a need to develop novel treatment approaches. P2Y₁ receptor (P2Y₁R) is a G protein-coupled nucleotide receptor. P2Y₁R is primarily coupled with the G_q protein; when the receptor combines with the ligand, it causes the activation of the G_q protein and then activates the downstream phospholipase C (PLC) signaling pathway. Regarding the tissue distribution of P2Y₁R and associated pathways, numerous studies have documented that P2Y₁Rs exert a physiological role in mediating CVDs. These findings indicate that P2Y₁R may serve as a potential molecular target for the treatment of CVDs. This review provides a detailed elucidation of the mechanisms by which P2Y₁R mediates cardiac fibrosis, thrombosis, atherosclerosis, platelet aggregation, hypertension, and vascular constriction and dilation. Furthermore, it summarizes novel P2Y₁R antagonists developed in recent years, laying a foundation for the subsequent structural optimization of P2Y₁R antagonists.

心血管疾病造成了巨大的社会负担。鉴于心血管疾病伴有多种并发症，传统的治疗方法不能完全治愈，有必要开发新的治疗方法。P2Y1受体（P2Y1R）是一种G蛋白偶联核苷酸受体。P2Y1R主要与Gq蛋白偶联；当受体与配体结合时，引起Gq蛋白的激活，进而激活下游磷脂酶C （PLC）信号通路。关于P2Y1R的组织分布及相关通路，大量研究证明P2Y1R在介导cvd中发挥生理作用。这些发现表明P2Y1R可能是治疗心血管疾病的潜在分子靶点。这篇综述详细阐述了P2Y1R介导心脏纤维化、血栓形成、动脉粥样硬化、血小板聚集、高血压和血管收缩和扩张的机制。并对近年来开发的新型P2Y1R拮抗剂进行了总结，为后续P2Y1R拮抗剂的结构优化奠定基础。

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引用次数: 0

Small molecule proteasome activation: comparative structural analysis of known stimulators 小分子蛋白酶体活化：已知刺激剂的比较结构分析。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry

Pub Date : 2025-11-05 DOI: 10.1016/j.bmc.2025.118470

Jaida M. Osman , Darci J. Trader

The proteasome is an enzyme complex which serves as the main machinery for protein degradation in eukaryotic cells. It has been demonstrated that the hydrolysis activity of the proteasome declines with age, leading to the disruption of proteostasis and the development of disease. Thus, increasing the activity of the proteasome could be beneficial to increase the health span of cells. The development of proteasome stimulators has been a major target for both better understanding the mechanism of protein degradation by the proteasome, as well as for developing therapies for certain diseases. Much is to be discovered about proteasome stimulation, but the field is limited by a lack of small molecules identified or developed for proteasome activation. Many currently available reported proteasome stimulators were initially developed for another therapeutic purpose. In this review, we have analyzed the structure of known proteasome stimulators to identify trends and important structural motifs could be used to develop more potent proteasome stimulators.

蛋白酶体是一种酶复合物，是真核细胞中蛋白质降解的主要机制。已经证明，蛋白酶体的水解活性随着年龄的增长而下降，导致蛋白酶平衡的破坏和疾病的发展。因此，增加蛋白酶体的活性可能有利于延长细胞的健康寿命。蛋白酶体刺激剂的开发已经成为更好地理解蛋白酶体降解蛋白质的机制以及开发某些疾病的治疗方法的主要目标。关于蛋白酶体的刺激还有很多有待发现的地方，但由于缺乏确定或开发用于蛋白酶体激活的小分子，这一领域受到限制。许多目前可用的蛋白酶体刺激剂最初是为了另一种治疗目的而开发的。在这篇综述中，我们分析了已知的蛋白酶体刺激剂的结构，以确定趋势和重要的结构基序，可以用来开发更有效的蛋白酶体刺激剂。

引用次数: 0

Tissue transglutaminase inhibitors over the past decade 组织转谷氨酰胺酶抑制剂的研究。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry

Pub Date : 2025-11-03 DOI: 10.1016/j.bmc.2025.118476

Brianna Ryan , Sarah Tribe , Jeffrey W. Keillor

Tissue transglutaminase (TG2) is a multifunctional protein that functions as a protein cross-linking enzyme and also as an intracellular G-protein. It has been implicated in numerous disorders such as celiac disease, fibrosis and different cancers. Due to these diverse pathologies, there is a need to develop a range of inhibitors that can target the different functionalities of TG2. In this review, we present the latest inhibitors published over the past decade, specifically focussing on irreversible inhibitors (peptidomimetic and small-molecule), probes, and reversible inhibitors.

组织转谷氨酰胺酶（Tissue transglutaminase, TG2）是一种多功能蛋白，具有蛋白质交联酶和细胞内g蛋白的功能。它与许多疾病有关，如乳糜泻、纤维化和不同的癌症。由于这些不同的病理，有必要开发一系列的抑制剂，可以针对TG2的不同功能。在这篇综述中，我们介绍了过去十年中发表的最新抑制剂，特别关注不可逆抑制剂（拟肽和小分子）、探针和可逆抑制剂。

引用次数: 0

Natural products that suppress 2-deoxy-d-glucose-induced cell death as potential drug seeds for mitochondrial diseases 抑制2-脱氧葡萄糖诱导的细胞死亡的天然产物作为线粒体疾病的潜在药物种子。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry

Pub Date : 2025-11-02 DOI: 10.1016/j.bmc.2025.118478

Koyo Honda , Yuki Hitora , Yusaku Sadahiro , Masahiro Wato , Yuriko Nagano , Sachiko Tsukamoto

Mitochondrial dysfunction is not only a known cause of mitochondrial disease but has also been implicated in diabetes and neurodegenerative diseases. Therefore, modulating mitochondrial function may provide new insights into the treatment of these diseases. In this study, we used a cancer cell-based energy metabolism restriction model with a glycolytic inhibitor and screened a natural product library and a fungal extract library to identify natural products that improve mitochondrial function. Seven compounds, including quillaic acid (1) and 20-deoxyingenol (2), were identified as mitochondrial function modulators from the Selleck natural product library. Furthermore, an extract of a fungus, Trichoderma sp., from an in-house fungal extract library suppressed 2-deoxy-d-glucose-induced cell death. Bioassay-guided fractionation of the extract afforded seven known sorbicillinoids. Among them, bisvertinol (8) did not directly affect cellular energy metabolism but appeared to protect mitochondria from oxidative stress through its antioxidant properties.

线粒体功能障碍不仅是线粒体疾病的已知原因，而且还与糖尿病和神经退行性疾病有关。因此，调节线粒体功能可能为这些疾病的治疗提供新的见解。在这项研究中，我们使用基于癌细胞的能量代谢限制模型和糖酵解抑制剂，筛选天然产物库和真菌提取物库，以确定改善线粒体功能的天然产物。从Selleck天然产物文库中鉴定出7个线粒体功能调节剂，其中包括棘酸(1)和20-脱氧ingenol(2)。此外，真菌的提取物，木霉sp.，从内部真菌提取物库抑制2-脱氧-d-葡萄糖诱导的细胞死亡。用生物测定法对提取物进行了分馏，得到了7种已知的山梨二醇类化合物。其中，bisvertinol(8)不直接影响细胞能量代谢，但似乎通过其抗氧化特性保护线粒体免受氧化应激。

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引用次数: 0