European Journal of Medicinal Chemistry Reports最新文献_第3页

Pharmacognosy and natural product chemistry of the marine sponge Hyrtios erectus 海绵的生药学及天然产物化学研究

European Journal of Medicinal Chemistry Reports

Pub Date : 2025-10-14 DOI: 10.1016/j.ejmcr.2025.100303

Christian Bailly

Marine-derived bioactive natural products are an essential resource for drug discovery. In particular, marine sponges and associated symbionts can be exploited to discover innovative compounds and new drug candidates. The sponge Hyrtios erectus which is largely distributed in Asian tropical areas, has been extensively investigated as a source of bioactive natural products. A detailed analysis of the natural products isolated from this sponge and their pharmacological properties has been performed. The study led to the identification of over 160 natural products, including over 50 alkaloids, 100 terpenoids and a few other compounds like phenolic alkenes (erectuseneols), chromanones (hyrtiosones) and cyclic peptides (spongitatin-1). The survey introduces multiple series of products, such as the hyrtiosins, hyrtiosulawesine, hyrtiazepine, hyrtioerectines, hyrtioreticulins, hyrtimomines, hyrtinadines, and hainanerectamines among the alkaloids. A large range of sesterterpenes and sesquiterpenes have been isolated, in particular scalarane-type sesterterpenoids such as erectascalaranes A-B, hyrtioscalaranes A-B and hyrtiosins A-F, in addition to a panoply of scalarin and scalaradial derivatives. All these compounds are presented together with their pharmacological properties. Synthetic procedures leading to some of these natural products and analogues are described, notably for hyrtiozulawesine, hyrtinadine A, hytiosine B, and salmahyrtisol A. At the pharmacological level, the most interesting products and associated molecular targets are discussed, such as the targeting of the orphan nuclear receptor Nur77 with 12-epi-scalaradial derivatives. An updated view of the chemical and pharmacological diversity associated with Hyrtios erectus is provided with the goal to promote further researches with this sponge erected as an emblematic figure of the marine natural product chemistry.

海洋生物活性天然产物是药物发现的重要资源。特别是，海洋海绵和相关的共生体可以用来发现创新的化合物和新的候选药物。海绵直立人（Hyrtios erectus）作为一种具有生物活性的天然产物，广泛分布于亚洲热带地区。从这种海绵中分离的天然产物及其药理特性进行了详细的分析。该研究鉴定了160多种天然产物，包括50多种生物碱，100多种萜类化合物和一些其他化合物，如酚烯（直立tuseneols），激素（hytiosones）和环肽（海绵蛋白-1）。该调查介绍了生物碱中hytiosins、hytisulawesine、hytiazepine、hytioerecines、hytioticulins、hytiomines、hytiadines、hainanectamines等多个系列产品。目前已分离出大量的半萜类和倍半萜类化合物，特别是角姜烷型的酯萜类化合物，如直链角姜烷A- b、杂环角姜烷A- b和杂环角苷A- f，此外还分离出大量的角姜素及其衍生物。所有这些化合物连同它们的药理学性质一起呈现。本文描述了一些天然产物和类似物的合成过程，特别是hytiozulawesine、hytiadine A、hytiosine B和salmahyrtisol A。在药理学水平上，讨论了最有趣的产物和相关的分子靶标，例如用12-外标径向衍生物靶向孤儿核受体Nur77。通过对直立人海绵的化学和药理多样性的最新认识，促进了对这种海绵的进一步研究，使其成为海洋天然产物化学的象征。

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引用次数: 0

Synthesis, bioactivity and docking studies of chrysin derivatives as iNOS inhibitors 金菊素衍生物作为iNOS抑制剂的合成、生物活性及对接研究

European Journal of Medicinal Chemistry Reports

Pub Date : 2025-10-04 DOI: 10.1016/j.ejmcr.2025.100301

Federica Falbo , Jessica Ceramella , Domenico Iacopetta , Nicola Gambacorta , Daniela Trisciuzzi , Orazio Nicolotti , Michele De Luca , Martina Chieffallo , Anna Ramunno , Daniela Bonofiglio , Lorenza Improta , Francesca Aiello , Maria Stefania Sinicropi

Endothelial dysfunction, mainly linked to ionic channel malfunctions, is a key mechanism in the pathogenesis of different vascular disorders including hypertension and atherosclerosis. Several studies confirm a strong correlation between endothelial dysfunction, inflammation and oxidative stress. Regular consumption of antioxidant polyphenol-rich foods has been linked to a reduction in cardiovascular morbidity and mortality. The flavone chrysin, a known Ca_v1.2 channel inhibitor, was selected in this work as lead compound to generate a library of its derivatives evaluated for their antioxidant and anti-inflammatory properties by means of vitro and cell-based assays. Among them, the best one resulted in the 8-nitrochrysin (1i). Molecular docking revealed that the nitro group plays a critical role in enhancing the binding mode toward iNOS by facilitating the formation of additional polar interactions compared to chrysin. LogP values of chrysin derivatives were also experimentally determined via spectrophotometric method to evaluate the impact of the chemical modifications with respect to the parent compound.

内皮功能障碍是高血压、动脉粥样硬化等多种血管疾病发病的重要机制，主要与离子通道功能障碍有关。几项研究证实内皮功能障碍、炎症和氧化应激之间有很强的相关性。经常食用富含抗氧化多酚的食物与降低心血管发病率和死亡率有关。黄酮菊花素是一种已知的Cav1.2通道抑制剂，本研究选择黄酮菊花素作为先导化合物，通过体外和细胞实验评估其衍生物的抗氧化和抗炎特性。其中效果最好的是8-硝基菊素（1i）。分子对接表明，与菊花素相比，硝基通过促进形成额外的极性相互作用，在增强与iNOS的结合模式中起着关键作用。用分光光度法测定了金菊素衍生物的LogP值，以评价化学修饰对母体化合物的影响。

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引用次数: 0

Targeted regulatory strategies for VCAM-1 in multisystem diseases VCAM-1在多系统疾病中的靶向调控策略

European Journal of Medicinal Chemistry Reports

Pub Date : 2025-09-27 DOI: 10.1016/j.ejmcr.2025.100300

Ruirong Peng , Yu Zhang , Zhenyu He , Yueling Pang , Huanhuan Ma , Ming Fang , Xiaoshan Ding , Yanan Wang , Zhihong Du , Fanming Kong , Liping Chen , Yongqi Liu , Ling Li , Jiawei Li

Systemic diseases are conditions caused by multiple factors (such as immune disorders, inflammation, tumors, etc.) that affect multiple organs, tissues, or systems throughout the body. These diseases are typically characterized by complex pathological states and diverse clinical symptoms. Vascular cell adhesion molecule-1 (VCAM-1) is a multifunctional transmembrane protein that plays a key role in various pathological processes, including inflammation, immune responses, and tumor progression, by mediating immune cell adhesion, regulating the tumor microenvironment, and facilitating signal transduction. This article aims to review the mechanistic roles of VCAM-1 in systemic diseases affecting the circulatory, respiratory, and digestive systems, as well as the association between VCAM-1 and tumor characteristics. Additionally, it discusses targeted therapeutic drugs (including traditional Chinese medicine and Western medicine) that regulate VCAM-1 for disease treatment, providing a theoretical basis for clinical research.

全身性疾病是由多种因素（如免疫紊乱、炎症、肿瘤等）引起的，影响全身多个器官、组织或系统的疾病。这些疾病的典型特点是病理状态复杂，临床症状多样。血管细胞粘附分子-1 （Vascular cell adhesion molecule-1, VCAM-1）是一种多功能跨膜蛋白，通过介导免疫细胞粘附、调节肿瘤微环境和促进信号转导，在炎症、免疫反应和肿瘤进展等多种病理过程中发挥关键作用。本文旨在综述VCAM-1在影响循环、呼吸和消化系统的系统性疾病中的机制作用，以及VCAM-1与肿瘤特征之间的关系。并探讨调控VCAM-1的靶向治疗药物（包括中药和西药）用于疾病治疗，为临床研究提供理论依据。

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引用次数: 0

Research progress of sustained-release microsphere technology in drug delivery 缓释微球技术在给药中的研究进展

European Journal of Medicinal Chemistry Reports

Pub Date : 2025-09-26 DOI: 10.1016/j.ejmcr.2025.100299

Tao-Tao Ge, Hai-Yan Guo, Chun-Mei Zhang, Shu-Feng Li

sustained-release microsphere technology, with its unique advantages of prolonged controlled release, enhanced therapeutic efficacy, reduced side effects, and improved patient compliance, has emerged as a research hotspot in modern drug delivery. This review systematically summarizes recent advances in sustained-release microspheres in the biomedical field. First, the core concepts and distinct advantages of this approach, compared with conventional drug administration, are elaborated. Subsequently, the principles and features of key preparation techniques, including emulsion–solvent evaporation, spray drying, and advanced microfluidic methods, are highlighted. Furthermore, the applications and validation of microsphere-based systems in diverse therapeutic areas—such as transarterial chemoembolization for cancer, chronic disease management (e.g., diabetes, psychiatric disorders), and local targeted therapies (e.g., ophthalmology, postoperative analgesia)—are critically discussed. Finally, the current challenges and future perspectives of this technology are outlined, providing insights for its further development and clinical translation.

缓释微球技术以其缓释时间延长、疗效提高、副作用减少、患者依从性提高等独特优势，成为现代给药领域的研究热点。本文系统综述了近年来缓释微球在生物医学领域的研究进展。首先，阐述了该方法相对于传统给药方式的核心概念和明显优势。随后，重点介绍了乳液-溶剂蒸发、喷雾干燥、先进微流控等关键制备技术的原理和特点。此外，微球系统在不同治疗领域的应用和验证——如经动脉化疗栓塞治疗癌症、慢性疾病管理（如糖尿病、精神疾病）和局部靶向治疗（如眼科、术后镇痛）——也进行了批判性的讨论。最后，概述了该技术目前面临的挑战和未来的前景，为其进一步发展和临床转化提供了见解。

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引用次数: 0

Halogen-containing NHC and bis-NHC silver complexes. Synthesis, structure and antimicrobial activity 含卤NHC和双NHC银配合物。合成、结构和抗菌活性

European Journal of Medicinal Chemistry Reports

Pub Date : 2025-09-23 DOI: 10.1016/j.ejmcr.2025.100298

Alexandr S. Avksentiev , Vagiz Sh Saberov , Svetlana V. Shishkina , Alexey B. Ryabitsky , Olena Z. Komarovska-Porokhnyavets , Vira I. Lubenets , Vitaliy A. Matvienko , Gennady F. Rayenko , Liubov M. Vakhitova , Nikolai I. Korotkikh

It was found that the in-situ reaction of halogen-containing imidazolium and benzimidazolium salts with silver nitrate, chloride, iodide or perchlorate in the presence of potassium carbonate leads to the corresponding monocarbene (NHC) (LAgX) and bis-NHC silver complexes (L₂AgX) including the first strongly sterically shielded bis-NHC complexes (IPr)₂AgX. In the presence of o-phenanthroline, carbene-phenanthroline complex (IPr∗)(phen)AgClO₄ was obtained. The reactions can be an addition to the known method of Lin with the use of silver oxide. The halogenide silver carbene complexes are also obtained by the exchange of the anion from the ionic perchlorate complexes to halogenide ions (Cl⁻, I⁻). The structure of the synthesized compounds is confirmed by the methods of ¹H and ¹³C NMR spectroscopy and for five compounds by the X-ray diffraction study. Most compounds have an ionic character in crystals and in solutions, even for the complex with a sterically shielded silver atom (IPr)₂AgNO₃ and monocarbene complexes. Synthesized complexes show high antibacterial (MIC up to 1.9 μg/mL on M. luteum) and antifungal activity (MIC up to 0.9 μg/mL on A. niger and 1.9 μg/mL on C. tenuis).

研究发现，含卤咪唑和苯并咪唑盐在碳酸钾存在下与硝酸银、氯化物、碘化物或高氯酸盐原位反应可生成相应的单碳（NHC）（LAgX）和双NHC银配合物（L2AgX），其中包括首个强空间屏蔽的双NHC配合物（IPr）2AgX。在邻菲罗啉存在下，得到了卡宾-菲罗啉配合物（IPr∗）（phen）AgClO4。这些反应可以作为已知的Lin方法的补充，使用氧化银。通过离子高氯酸盐配合物中的阴离子交换卤化物离子（Cl−,I−），也可以得到卤化银碳配合物。合成化合物的结构通过1H和13C核磁共振谱法和x射线衍射研究得到证实。大多数化合物在晶体和溶液中都具有离子性质，甚至对于具有空间屏蔽银原子（IPr）的配合物（2AgNO3）和单羰基配合物也是如此。合成的配合物具有较高的抑菌活性（对黄体霉的MIC可达1.9 μg/mL）和抗真菌活性（对黑曲霉的MIC可达0.9 μg/mL，对黄曲霉的MIC可达1.9 μg/mL）。

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引用次数: 0

Protective effects of Sacha inchi meal protein hydrolysate against oxidative stress and endothelial dysfunction via MDA suppression and SOD activation in L-NAME-induced hypertensive rats 核桃粕蛋白水解物通过抑制MDA和激活SOD对l - name诱导的高血压大鼠氧化应激和内皮功能障碍的保护作用

European Journal of Medicinal Chemistry Reports

Pub Date : 2025-09-13 DOI: 10.1016/j.ejmcr.2025.100297

Pakaporn Sa-nguanpong , Paweena Wetprasit , Usana Chatturong , Krongkarn Chootip , Napapas Kantip , Worasit Tochampa , Khanitta Ruttarattanamongkol , Tippaporn Bualeong

Endothelial dysfunction and oxidative stress are central contributors to hypertension. Sacha inchi meal protein hydrolysate (SIPH) is recognized for its strong antioxidant activity and potential cardiovascular benefits. This study investigated the protective effects of SIPH on endothelial function and oxidative stress in rats with L-NAME (LN)-induced hypertension. Acute oral toxicity testing showed an LD₅₀ greater than 5000 mg/kg, classifying SIPH as low hazard (Category 5). Male Sprague-Dawley rats received LN (40 mg/kg) and were treated orally with SIPH (100, 300, or 500 mg/kg), captopril (5 mg/kg), or SIPH (500 mg/kg) combined with captopril (2.5 mg/kg) for five weeks. Blood pressure was monitored weekly and validated by carotid artery cannulation. Endothelial function was assessed by vasorelaxation responses to acetylcholine (ACh) and sodium nitroprusside (SNP) in isolated aortic rings, while serum malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured as markers of oxidative stress. LN administration elevated blood pressure impaired ACh-induced vasorelaxation, increased MDA, and reduced SOD activity. SIPH at 500 mg/kg significantly reduced blood pressure, restored endothelial-dependent relaxation, decreased lipid peroxidation, and enhanced antioxidant defense. Notably, the combination of SIPH with captopril exerted synergistic antihypertensive effects, producing greater improvements in vascular reactivity and oxidative balance than either treatment alone. These findings demonstrate that SIPH is a potent vascular protector, acting through synergistic antihypertensive, vasodilatory, and antioxidant mechanisms. Its properties position SIPH as a promising natural dietary intervention for mitigating hypertension and preserving endothelial function.

内皮功能障碍和氧化应激是高血压的主要诱因。杉树粕蛋白水解物（SIPH）被认为具有很强的抗氧化活性和潜在的心血管益处。本研究探讨了SIPH对L-NAME （LN）诱导的高血压大鼠内皮功能和氧化应激的保护作用。急性口服毒性测试显示LD50大于5000 mg/kg，将SIPH归类为低危害（第5类）。雄性sprap - dawley大鼠接受LN (40 mg/kg)，并口服SIPH（100、300或500 mg/kg）、卡托普利（5 mg/kg）或SIPH （500 mg/kg）联合卡托普利（2.5 mg/kg） 5周。每周监测血压，并通过颈动脉插管进行验证。通过血管对乙酰胆碱（ACh）和硝普钠（SNP）的松弛反应来评估内皮功能，同时测定血清丙二醛（MDA）和超氧化物歧化酶（SOD）活性作为氧化应激的标志物。LN使血压升高，损伤了乙酰胆碱引起的血管松弛，增加了丙二醛，降低了SOD活性。500 mg/kg SIPH可显著降低血压，恢复内皮依赖性松弛，降低脂质过氧化，增强抗氧化防御。值得注意的是，SIPH联合卡托普利具有协同降压作用，比单独治疗更能改善血管反应性和氧化平衡。这些发现表明SIPH是一种有效的血管保护者，通过协同抗高血压、血管舒张和抗氧化机制起作用。它的特性使SIPH成为一种有希望的天然饮食干预，可以减轻高血压和保持内皮功能。

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引用次数: 0

Development of highly potent and selective oncogenic KRASG12D PROTAC degraders 高效和选择性致癌KRASG12D PROTAC降降剂的开发

European Journal of Medicinal Chemistry Reports

Pub Date : 2025-08-30 DOI: 10.1016/j.ejmcr.2025.100296

Yaqiu Mao , Pengli Wei , Ting Wei , Yalei Wang , Zhenze Qi , Xu Cai , Changkai Jia , Zhiyuan Zhao , Bingkun Li , Min Qiao , Yaxin Zou , Zhihui Mu , Xiaofang Lei , Tingting Yang , Shiyang Sun , Xuesong Feng , Pengyun Li , Zhibing Zheng

As a key driver of tumorigenesis and cancer development, the KRAS^G12D mutation is ubiquitous existed in KRAS-associated malignancies, highlighting the urgent clinical need for effective KRAS^G12D targeting drugs. In this study, through rational design and multiple cell type-based antiproliferative evaluation, we identified a novel KRAS^G12D inhibitor, Y-I-1, which demonstrated remarkable anti-cancer activity. Subsequent computational analyses including molecular dynamics (MD) simulations, binding free energy calculations, umbrella sampling, and protein-ligand docking revealed its excellent binding characteristics, rationalizing the observed potency. Building upon the structure of Y-I-1, we constructed proteolysis-targeting chimera (PROTAC) by conjugating it with different linker moieties and VH032. Among them, degrader Y-D-2 potently and selectively exhibited nanomolar inhibitory IC₅₀, degradation DC₅₀ values, and more than 95 % maximum degradation (D_max) in KRAS^G12D-mutant cancer cells via ubiquitin proteasome-involving pathway, accompanied by nanomolar IC₅₀ efficiency for phosphorylated ERK (pERK) inhibition. Mechanistically, Y-D-2 significantly induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, Y-D-2 led to significant tumor growth inhibition in the GP2D xenograft model with well-tolerated dose-schedules with favorable PK properties. This study not only provides an important theoretical basis for the optimal design of KRAS^G12D degraders, but also highlights its potential for the treatment of KRAS^G12D-driven cancers.

KRASG12D突变作为肿瘤发生和癌症发展的关键驱动因素，在kras相关恶性肿瘤中普遍存在，迫切需要临床有效的KRASG12D靶向药物。本研究通过合理设计和基于多细胞类型的抗增殖评价，我们鉴定出一种新的KRASG12D抑制剂Y-I-1，它具有显著的抗癌活性。随后的计算分析包括分子动力学（MD）模拟、结合自由能计算、保护伞取样和蛋白质配体对接，揭示了其良好的结合特性，使所观察到的效力更加合理。在Y-I-1结构的基础上，我们将其与不同的连接体片段和VH032偶联，构建了蛋白水解靶向嵌合体（PROTAC）。其中，降解剂Y-D-2在krasg12d突变的癌细胞中，通过泛素蛋白酶体参与途径，有效且选择性地表现出纳米摩尔抑制IC50、降解DC50值和超过95%的最大降解（Dmax），同时具有纳米摩尔抑制磷酸化ERK （pERK）的IC50效率。在机制上，Y-D-2显著诱导细胞凋亡、G1细胞周期阻滞、抑制细胞迁移和侵袭。值得注意的是，Y-D-2在GP2D异种移植模型中具有显著的肿瘤生长抑制作用，具有良好的耐受性和良好的PK特性。本研究不仅为KRASG12D降解物的优化设计提供了重要的理论依据，同时也凸显了KRASG12D驱动型癌症的治疗潜力。

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引用次数: 0

Molecules with alkyne fragment in medicinal chemistry: The path from neurotoxins to drugs 药物化学中的炔片段分子：从神经毒素到药物的途径

European Journal of Medicinal Chemistry Reports

Pub Date : 2025-08-18 DOI: 10.1016/j.ejmcr.2025.100294

Nataliya Zelisko , Roman Lesyk

In this comprehensive review, we explore a diverse array of highly promising compounds, categorized based on their pharmacological properties, origins, and synthetic methodologies, to highlight the critical role of alkyne functionalities in advancing medicinal chemistry. Our analysis underscores the unique contributions of acetylene-containing compounds, emphasizing their structural significance and therapeutic potential.

The remarkable versatility of acetylene-bearing molecules is evident in their wide-ranging biological activities, which position them as exceptional candidates for drug development. Extensive studies compiled in this review demonstrate that incorporating an acetylene group into molecular frameworks significantly enhances bioactivity. Numerous naturally occurring alkynes exhibit potent antibacterial, antifungal, and anticancer effects. Notably, compounds featuring a propargylamine group are established inhibitors of monoamine oxidase (MAO) and cholinesterases (ChEs). Additionally, a range of alkyne derivatives shows promise as H3-receptor antagonists, offering potential treatments for conditions such as epilepsy, depression, schizophrenia, Parkinson's disease, Alzheimer's disease, sleep disorders, attention deficit hyperactivity disorder, and various inflammatory and gastrointestinal disorders. Acetylene-containing compounds also play a role in anti-HIV therapies, with certain synthetic steroids falling within this class. Furthermore, alkynes are integral to multi-target-directed ligand (MTDL) strategies, broadening their therapeutic applications.

A particular focus of this review is the compelling anticancer potential of MAO inhibitors, which have garnered significant attention from pharmaceutical companies for their efficacy against prostate cancer, Hodgkin lymphoma, glioma brain tumors, non-small cell lung cancer, A-2058 melanoma cell lines, and acute myeloid leukemia. This has spurred interest in drug repurposing, establishing these compounds as a cornerstone of innovative therapeutic development.

在这篇全面的综述中，我们根据其药理性质、来源和合成方法对各种极具前景的化合物进行了分类，以突出炔官能团在推进药物化学中的关键作用。我们的分析强调了含乙炔化合物的独特贡献，强调了它们的结构意义和治疗潜力。含乙炔分子的显著多功能性在其广泛的生物活性中是显而易见的，这使它们成为药物开发的特殊候选者。大量的研究表明，在分子框架中加入乙炔基团可以显著提高生物活性。许多天然存在的炔具有强大的抗菌、抗真菌和抗癌作用。值得注意的是，含有丙胺基团的化合物是单胺氧化酶（MAO）和胆碱酯酶（ChEs）的抑制剂。此外，一系列炔衍生物显示出作为h3受体拮抗剂的前景，为癫痫、抑郁症、精神分裂症、帕金森病、阿尔茨海默病、睡眠障碍、注意缺陷多动障碍以及各种炎症和胃肠道疾病等疾病提供潜在的治疗方法。含乙炔的化合物也在抗hiv治疗中发挥作用，某些合成类固醇就属于这一类。此外，炔烃是多靶点定向配体（MTDL）策略的组成部分，扩大了它们的治疗应用。本综述的一个特别重点是MAO抑制剂的抗癌潜力，由于其对前列腺癌、霍奇金淋巴瘤、胶质瘤脑肿瘤、非小细胞肺癌、A-2058黑色素瘤细胞系和急性髓性白血病的疗效，引起了制药公司的极大关注。这激发了人们对药物再利用的兴趣，使这些化合物成为创新治疗发展的基石。

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引用次数: 0

Cheminformatics in advancing dengue antiviral research: From conventional molecular modeling (MM) to current artificial intelligence (AI) approaches 化学信息学在推进登革热抗病毒研究中的作用：从传统的分子建模（MM）到当前的人工智能（AI）方法

European Journal of Medicinal Chemistry Reports

Pub Date : 2025-08-16 DOI: 10.1016/j.ejmcr.2025.100295

Rinki Prasad Bhagat , Sk Abdul Amin , Lucia Sessa , Simona Concilio , Stefano Piotto , Shovanlal Gayen

Cheminformatics has rapidly evolved and garnered widespread attention due to its potential to accelerate the process and reduce the cost of drug design and development. These technologies play a crucial role in drug design against dengue virus (DENV), a neglected tropical disease that remains a significant global health burden, with millions of cases reported annually. Recent advancements in cheminformatics and artificial intelligence (AI)-driven approaches offer promising strategies for designing inhibitors targeting key viral proteins. This study explores the applications of various cheminformatics methods, including conventional molecular modeling (pharmacophore mapping, molecular docking, molecular dynamics (MD) simulations, virtual screening), and artificial intelligence (AI)/machine learning (ML)-based strategies reported to identify compounds with high affinity and specificity for critical DENV protein targets. Additionally, it highlights the synergy between experimental validation, and in silico predictions to prioritize candidate molecules for further development.

化学信息学迅速发展，并引起了广泛的关注，因为它有可能加快过程，降低药物设计和开发的成本。这些技术在针对登革热病毒（DENV）的药物设计中发挥着至关重要的作用。登革热病毒是一种被忽视的热带病，仍然是全球重大的卫生负担，每年报告有数百万病例。化学信息学和人工智能（AI）驱动方法的最新进展为设计针对关键病毒蛋白的抑制剂提供了有前途的策略。本研究探索了各种化学信息学方法的应用，包括传统的分子建模（药效团定位、分子对接、分子动力学（MD）模拟、虚拟筛选），以及基于人工智能(AI)/机器学习（ML）的策略，以识别对关键DENV蛋白靶点具有高亲和力和特异性的化合物。此外，它强调了实验验证和计算机预测之间的协同作用，以优先考虑候选分子以进一步开发。

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引用次数: 0

Screening of G-quadruplex DNA ligands by fluorescence detection of peptide displacement 利用肽位移荧光检测筛选g -四重体DNA配体

European Journal of Medicinal Chemistry Reports

Pub Date : 2025-08-07 DOI: 10.1016/j.ejmcr.2025.100293

Valentina Arciuolo , Simona Marzano , Rossella Buono, Nicola Grasso, Anna Di Porzio, Antonio Randazzo, Bruno Pagano, Jussara Amato

G-quadruplexes (G4s) are noncanonical DNA/RNA structures involved in key cellular processes, and their interactions with proteins are emerging as therapeutic targets. However, strategies to identify ligands that bind G4s and potentially modulate these interactions remain limited. Here, we describe a fluorescence-based assay for rapid, quantitative evaluation of small molecules that bind G4s and potentially interfere with protein recognition. The method employs a fluorophore-labeled peptide derived from a conserved G4-binding protein motif, and a G4-forming sequence labeled with a fluorescence acceptor. Ligand-induced peptide displacement is detected via fluorescence increase. A panel of known G4 ligands was tested, and results correlated with binding affinities. A duplex DNA competition assay further assessed ligand selectivity. This method provides a scalable tool for screening G4 ligands with ability to compete with G4-recognition motifs, supporting drug discovery efforts.

g -四plex （G4s）是参与关键细胞过程的非规范DNA/RNA结构，它们与蛋白质的相互作用正成为治疗靶点。然而，鉴定结合G4s并可能调节这些相互作用的配体的策略仍然有限。在这里，我们描述了一种基于荧光的检测方法，用于快速定量评估结合G4s并可能干扰蛋白质识别的小分子。该方法采用从保守的g4结合蛋白基序衍生的荧光团标记肽，以及用荧光受体标记的g4形成序列。通过荧光增加检测配体诱导的肽位移。对一组已知的G4配体进行了测试，结果与结合亲和力相关。双链DNA竞争分析进一步评估了配体的选择性。该方法提供了一种可扩展的工具，用于筛选具有与G4识别基序竞争能力的G4配体，支持药物发现工作。

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引用次数: 0