Medicine in Drug Discovery最新文献_第4页

Corrigendum to “Neutralization of systemic toxicity of Daboia russelii venom and reprotoxin fraction by IgY antibodies” [Med. Drug Discov. 27 (2025) 100217] “IgY抗体中和rusbiia russelii毒液和生殖原蛋白部分的全身毒性”的勘误表[Med. Drug discovery . 27 (2025) 100217]

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2025-08-08 DOI: 10.1016/j.medidd.2025.100219

Punithkumar Naraganahalli Krishnaraj , Kiran Kumar Mudnakudu-Nagaraju , Nagalambika Prasad , Chandavi Venkatesh , Deekshith Ramesh , Druthi Venktesh , Anusha Chikkamandagere Kumar , Kumar Jajur Ramanna

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Serum albumin nanoparticles: Ligand functionalization for enhanced targeted therapeutics in precision medicine 血清白蛋白纳米颗粒：配体功能化在精准医学中增强靶向治疗

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2025-07-26 DOI: 10.1016/j.medidd.2025.100218

Sakshi Shahapurmath, Bhuvaneshwari R. Sharannavar, Rahul Koli

Serum albumin-based nanoparticles, derived from bovine (BSA) and human (HSA) sources, have emerged as versatile carriers in drug delivery systems due to their intrinsic biocompatibility, biodegradability, and amenability to surface modification. This review provides a comprehensive analysis of recent advancements in the functionalization of albumin nanoparticles with diverse ligands to enhance targeting specificity and therapeutic efficacy. Functional moieties such as folic acid, peptides, aptamers, antibodies and their fragments, polymers, chitosan, hyaluronic acid, biotin, transferrin, cholesterol, surfactants, and apolipoproteins have been extensively explored for their role in modulating cellular uptake, drug release kinetics, and site-specific accumulation. A systematic discussion of ligand selection, conjugation strategies, and encapsulated therapeutics is presented, along with a comprehensive evaluation of in vitro and in vivo studies assessing the pharmacokinetics, biodistribution, and therapeutic potential of ligand modified albumin nanoparticles. Particular empHSAis is placed on the applications of functionalized albumin nanoparticles in oncology, inflammatory and neurological disorders, and infectious diseases. Emerging trends highlight the development of multifunctional nanocarriers integrating imaging agents for theranostic applications and the application of cutting-edge functionalization techniques to facilitate personalized medicine. This review serves as a critical resource for researchers, fostering advancements in the rational design and optimization of albumin-based nanocarriers for precision drug delivery.

基于血清白蛋白的纳米颗粒来源于牛（BSA）和人（HSA），由于其内在的生物相容性、生物可降解性和表面修饰性，已成为药物输送系统中的多功能载体。本文综述了利用不同配体功能化白蛋白纳米颗粒以提高靶向特异性和治疗效果的最新进展。叶酸、多肽、适体、抗体及其片段、聚合物、壳聚糖、透明质酸、生物素、转铁蛋白、胆固醇、表面活性剂和载脂蛋白等功能基团在调节细胞摄取、药物释放动力学和位点特异性积累中的作用已被广泛探索。本文对配体选择、偶联策略和封装疗法进行了系统的讨论，并对配体修饰白蛋白纳米颗粒的体内和体外研究进行了全面的评估，以评估其药代动力学、生物分布和治疗潜力。特别强调功能化白蛋白纳米颗粒在肿瘤学、炎症和神经系统疾病以及传染病中的应用。新兴趋势突出了多功能纳米载体的发展，将成像剂集成到治疗应用中，并应用尖端功能化技术来促进个性化医疗。这篇综述为研究人员提供了重要的资源，促进了基于白蛋白的纳米载体的合理设计和优化，以实现精确的药物递送。

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引用次数: 0

Neutralization of systemic toxicity of Daboia russelii venom and reprotoxin fraction by IgY antibodies IgY抗体中和大鲵毒液及生殖道原蛋白部分的全身毒性

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2025-07-18 DOI: 10.1016/j.medidd.2025.100217

Punithkumar Naraganahalli Krishnaraj , Kiran Kumar Mudnakudu-Nagaraju , Nagalambika Prasad , Chandavi Venkatesh , Deekshith Ramesh , Druthi Venktesh , Anusha Chikkamandagere Kumar , Kumar Jajur Ramanna

Daboia russelii, a highly venomous snake prevalent in South Asia, causes significant morbidity and mortality due to its complex venom, which includes neurotoxins, hemotoxins, and reprotoxins. Current equine-derived antivenoms, while effective, are associated with adverse effects like serum sickness. This study explores the potential of chicken-derived IgY antibodies as a safer, cost-effective alternative. Venom was fractionated using gel filtration chromatography, yielding six protein peaks, with Peak-I (large molecular weight fraction, LMF) and Peak-II (reprotoxin) used for immunization and neutralization studies. IgY antibodies raised against LMF in hens effectively neutralized twice the LD₅₀ dose of reprotoxin (1:4 ratio) and whole venom (1:8 ratio), mitigating neurotoxicity, edema, hemolysis, anticoagulation, proteolysis, and cytotoxicity. Compared to equine antivenoms, IgY showed comparable neutralization efficacy with potentially fewer side effects, highlighting its therapeutic promise. These findings suggest IgY antibodies merit further investigation as a novel antivenom for D. russelii envenomation.

Daboia russelii是一种普遍存在于南亚的高毒性蛇，由于其复杂的毒液，包括神经毒素，血液毒素和生殖原毒素，导致严重的发病率和死亡率。目前的马源抗蛇毒血清虽然有效，但与血清病等不良反应有关。本研究探讨了鸡源性IgY抗体作为一种更安全、成本效益更高的替代品的潜力。用凝胶过滤层析法分离毒液，得到6个蛋白峰，其中峰i（大分子质量分数，LMF）和峰ii （reprotoxin）用于免疫和中和研究。母鸡抗LMF的IgY抗体能有效中和2倍于LD50剂量的reprotoxin（1:4）和全毒（1:8），减轻神经毒性、水肿、溶血、抗凝、蛋白水解和细胞毒性。与马抗蛇毒血清相比，IgY显示出相当的中和效果，潜在的副作用更少，突出了其治疗前景。这些发现表明IgY抗体作为一种新的抗鲟毒血清值得进一步研究。

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引用次数: 0

Impact of CYP3A5 rs776746 and CYP3A7 rs2257401 polymorphism on steroid metabolism and dose optimization in pediatric nephrotic syndrome CYP3A5 rs776746和CYP3A7 rs2257401多态性对儿童肾病综合征类固醇代谢及剂量优化的影响

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2025-07-08 DOI: 10.1016/j.medidd.2025.100216

Praveenkumar Kochuthakidiyel Suresh , Yogalakshmi Venkatachalapathy , Nandita Ganesh , George Priya Doss C , Sangeetha Geminiganesan , Sudha Ekambaram , Mohana Priya C.D

A multicentric genetic study was conducted on 200 paediatric patients with nephrotic-range proteinuria, including 100 cases each of steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS). The study analysed two genetic variants: CYP3A5 (rs776746) and CYP3A7 (rs2257401). For CYP3A5 Variant rs776746 A > G is also known as 6986A > G CYP3A5*3 allele. Individuals with the A allele (6986A) carry the CYP3A5*1 (functional) allele. Individuals with the G allele (6986G) carry the CYP3A5*3 (non-functional) allele. overall genotype frequencies were 20.5 % AA, 30 % GG, and 49.5 % AG. In the SSNS group, the distribution was 13 % AA, 36 % GG, and 51 % AG (A allele: 0.38, G allele: 0.62), while the SRNS group showed 28 % AA, 24 % GG, and 48 % AG (A allele: 0.52, G allele: 0.48). For CYP3A7 rs2257401, genotype frequencies were 15 % GG, 21 % CC, and 64 % GC. In SSNS, 14 % were GG, 24 % CC, and 62 % GC; in SRNS, 16 % GG, 18 % CC, and 66 % GC. G and C allele frequencies were equal (0.5) in both groups for CYP3A7. The findings suggest that CYP3A5 rs776746, particularly the GG genotype, may be associated with reduced steroid response, potentially requiring alternative treatment approaches in SRNS patients. The rs776746 polymorphism involves an A > G substitution, where the AA genotype (CYP3A5 3/3) indicates non-functional enzyme expression. Genotypic comparison showed higher AA frequency in SRNS patients. The AA genotype was associated with lower steroid metabolism, necessitating dose reduction. In contrast, CYP3A7 rs2257401 showed no significant correlation. This suggests that CYP3A5 genotyping could aid dose optimization in steroid-resistant cases.

对200例肾病性蛋白尿患儿进行了多中心遗传研究，其中类固醇敏感性肾病综合征（SSNS）和类固醇耐药性肾病综合征（SRNS）各100例。该研究分析了两种遗传变异：CYP3A5 （rs776746）和CYP3A7 （rs2257401）。CYP3A5 Variant rs776746 A >；G也被称为6986A >；G CYP3A5*3等位基因。携带A等位基因（6986A）的个体携带CYP3A5*1（功能性）等位基因。具有G等位基因（6986G）的个体携带CYP3A5*3（非功能性）等位基因。总体基因型频率为20.5% AA， 30% GG和49.5% AG。SSNS组为13% AA、36% GG、51% AG (A等位基因：0.38，G等位基因：0.62)，而SRNS组为28% AA、24% GG、48% AG （A等位基因：0.52，G等位基因：0.48）。对于CYP3A7 rs2257401，基因型频率为15% GG， 21% CC和64% GC。SSNS中，GG占14%，CC占24%，GC占62%；SRNS中GG为16%，CC为18%，GC为66%。两组CYP3A7基因G和C等位基因频率相等（0.5）。研究结果表明，CYP3A5 rs776746，特别是GG基因型，可能与类固醇反应降低有关，可能需要替代SRNS患者的治疗方法。rs776746多态性涉及A >；G置换，其中AA基因型（CYP3A5 3/3）表明无功能酶表达。基因型比较显示SRNS患者AA频率较高。AA基因型与较低的类固醇代谢有关，需要减少剂量。相比之下，CYP3A7 rs2257401无显著相关性。这表明CYP3A5基因分型可以帮助优化类固醇耐药病例的剂量。

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引用次数: 0

Repositioning of rhodanine-thiazole hybrids as aldose reductase inhibitors 罗丹宁-噻唑杂交种醛糖还原酶抑制剂的重新定位

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2025-07-07 DOI: 10.1016/j.medidd.2025.100215

Shankar Gharge, Shankar G. Alegaon, Shriram D. Ranade, Rohini S. Kavalapure

This study investigates the aldose reductase (AR) inhibitory potential of a series of synthesized rhodanine-thiazole hybrids (7a–7 l) through a combination of biological assays and computational modeling. The derivatives were divided into two categories: rhodanine (7a–7f) and rhodanine acetic acid derivatives (7g–7l). Biological evaluation revealed that rhodanine acetic acid derivatives demonstrated superior AR inhibition, with IC₅₀ values ranging from 6.87 to 9.07 µM, compared to rhodanine derivatives (11.79–15.90 µM). Among them, compound 7i (4-fluoro rhodanine acetic acid) exhibited the highest potency (IC₅₀ = 6.87 ± 1.22 µM), outperforming the standard Quercetin. Kinetic studies confirmed 7i as a reversible, non-competitive inhibitor (Ki = 6.87 µM), indicating interaction at an allosteric site of AR. Molecular docking using Schrödinger’s Glide XP mode against AKR1B1 (PDB ID: 4JIR) revealed that 7i had the most favorable docking score (−10.02) and binding energy (−67.51 kcal/mol), surpassing the standard inhibitor Epalrestat. Molecular dynamics simulations (200 ns) for 7 h and 7i indicated stable binding within the active site, with TRP111 identified as a key interacting residue. Interaction profiling revealed consistent hydrogen bonding and hydrophobic interactions, especially for 7i. Further, Principal Component Analysis (PCA) and Free Energy Landscape (FEL) analysis confirmed the stability of the 7i-bound complex, showing a dominant low-energy conformation. Dynamic Cross-Correlation Matrix (DCCM) analysis suggested that 7i enhances protein stability by modulating internal dynamics. Overall, 7i emerges as a promising AR inhibitor with potential therapeutic relevance for diabetic complications.

本研究通过生物实验和计算模型相结合的方法研究了一系列合成的罗丹宁-噻唑杂交种（7a - 7l）的醛糖还原酶（AR）抑制潜力。衍生物分为罗丹宁（7a-7f）和罗丹宁乙酸衍生物（7g-7l）两类。生物学评价显示，罗丹宁乙酸衍生物的IC50值为6.87 ~ 9.07µM，优于罗丹宁衍生物（11.79 ~ 15.90µM）。其中化合物7i（4-氟罗丹宁乙酸）效价最高（IC50 = 6.87±1.22µM），优于标准槲皮素。动力学研究证实7i是一种可逆的非竞争性抑制剂（Ki = 6.87µM），表明在AR的变抗位点发生相互作用。利用Schrödinger的Glide XP模式对AKR1B1 （PDB ID: 4JIR）进行分子对接，7i具有最有利的对接评分（- 10.02）和结合能（- 67.51 kcal/mol），超过了标准抑制剂Epalrestat。分子动力学模拟（200 ns） 7 h和7i表明在活性位点内稳定结合，TRP111被鉴定为关键的相互作用残基。相互作用谱显示了一致的氢键和疏水相互作用，尤其是7i。主成分分析（PCA）和自由能分析（FEL）进一步证实了7i键配合物的稳定性，显示出主要的低能构象。动态相互关联矩阵（DCCM）分析表明，7i通过调节内部动态来增强蛋白质的稳定性。总之，7i是一种很有前景的AR抑制剂，对糖尿病并发症具有潜在的治疗意义。

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引用次数: 0

Flavonoids and anxiety: decoding their role in brain function and pathophysiology 类黄酮与焦虑：解码它们在脑功能和病理生理中的作用

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2025-07-02 DOI: 10.1016/j.medidd.2025.100214

Riya Singla , Sonia Kamboj , Brijesh Kumar Duvey , Anurag Bhargava , Jasmine Chaudhary

Anxiety disorder ranks among the most common mental health issues globally, thereby emphasizing the pressing necessity for the development of safer and more effective treatment alternatives. A noteworthy class of compounds in this context is flavonoids, which are naturally polyphenolic substances found in abundance within fruits, vegetables, and various medicinal plants. These compounds have garnered attention as candidates for the modulation of behaviours associated with anxiety. Examining the neurological mechanisms that underlie the anxiolytic effects of flavonoids reveals significant interaction with essential neurotransmitter systems. Specifically, engagement with serotonergic and dopaminergic pathways has been observed, indicating the multifaceted nature of flavonoids’ influence on anxiety responses. The biological activities, including antioxidant, anti-inflammatory properties, contribute to an additional layer to the potential therapeutic effect. Therefore, this review mainly focuses on the pathological facets of anxiety and explores the possible mechanism of flavonoids with the preclinical and clinical aspects for curing anxiety. Moreover, a growing body of experimental and clinical evidence indicates that certain flavonoids, including apigenin, quercetin, and luteolin, possess a considerable capacity to mitigate symptoms of anxiety, frequently resulting in a reduced incidence of adverse effects relative to traditional pharmacological therapies. This body of work reinforces the proposition that flavonoids may serve as viable natural alternatives to supplementary treatments in the management of anxiety disorders. Nevertheless, it remains imperative that additional research is conducted to clarify the mechanisms underlying the pharmacological effects of these flavonoids. Furthermore, investigations aimed at optimizing their bioavailability and validating clinical efficacy through extensive human trials are essential to fully ascertain their therapeutic potential in anxiety management.

焦虑症是全球最常见的精神健康问题之一，因此，迫切需要开发更安全、更有效的治疗方案。在这种情况下，一类值得注意的化合物是类黄酮，它是一种天然的多酚物质，在水果、蔬菜和各种药用植物中含量丰富。这些化合物作为与焦虑相关的行为调节的候选物引起了人们的注意。研究黄酮类化合物抗焦虑作用的神经机制揭示了其与基本神经递质系统的重要相互作用。具体而言，已观察到与血清素能和多巴胺能通路的参与，表明类黄酮对焦虑反应的影响具有多方面的性质。生物活性，包括抗氧化，抗炎特性，有助于额外的一层潜在的治疗效果。因此，本文主要从焦虑的病理方面进行综述，并从临床前和临床方面探讨类黄酮治疗焦虑的可能机制。此外，越来越多的实验和临床证据表明，某些类黄酮，包括芹菜素、槲皮素和木犀草素，具有相当大的缓解焦虑症状的能力，与传统的药物治疗相比，往往导致不良反应的发生率降低。这项工作强化了黄酮类化合物可能作为焦虑障碍管理补充治疗的可行的天然替代品的主张。然而，仍有必要进行更多的研究来阐明这些类黄酮的药理作用机制。此外，旨在优化其生物利用度和通过广泛的人体试验验证临床疗效的研究对于充分确定其在焦虑管理中的治疗潜力至关重要。

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引用次数: 0

Generative AI for drug discovery and protein design: the next frontier in AI-driven molecular science 用于药物发现和蛋白质设计的生成式人工智能：人工智能驱动的分子科学的下一个前沿

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2025-07-01 DOI: 10.1016/j.medidd.2025.100213

Uddalak Das

Generative artificial intelligence (AI) has emerged as a disruptive paradigm in molecular science, enabling algorithmic navigation and construction of chemical and proteomic spaces through data-driven modeling. This review systematically delineates the theoretical underpinnings, algorithmic architectures, and translational applications of deep generative models—including variational autoencoders (VAEs), generative adversarial networks (GANs), autoregressive transformers, and score-based denoising diffusion probabilistic models (DDPMs)—in the rational design of bioactive small molecules and functional proteins. We examine the role of latent space learning, probabilistic manifold exploration, and reinforcement learning in inverse molecular design, focusing on optimization of pharmacologically relevant objectives such as ADMET profiles, synthetic accessibility, and target affinity. Furthermore, we survey advancements in graph-based molecular generative frameworks, LLM-guided protein sequence modeling, and diffusion-based structural prediction pipelines (e.g., RFdiffusion, FrameDiff), which have demonstrated state-of-the-art performance in de novo protein engineering and conformational sampling. Generative AI is also catalyzing a paradigm shift in structure-based drug discovery via AI-augmented molecular docking (e.g., DiffDock), end-to-end binding affinity prediction, and quantum chemistry-informed neural potentials. We explore the convergence of generative models with Bayesian retrosynthesis planners, self-supervised pretraining on ultra-large chemical corpora, and multimodal integration of omics-derived features for precision therapeutics. Finally, we discuss translational milestones wherein AI-designed ligands and proteins have progressed to preclinical and clinical validation, and speculate on the synthesis of generative AI, closed-loop automation, and quantum computing in future autonomous molecular design ecosystems.

生成式人工智能（AI）已经成为分子科学领域的一个颠覆性范例，通过数据驱动的建模，实现了化学和蛋白质组学空间的算法导航和构建。本文系统地描述了深层生成模型的理论基础、算法架构和转化应用，包括变分自编码器（VAEs）、生成对抗网络（GANs）、自回归变压器和基于分数的去噪扩散概率模型（ddpm），这些模型在合理设计生物活性小分子和功能蛋白方面的应用。我们研究了潜在空间学习、概率流形探索和强化学习在逆分子设计中的作用，重点是优化药理学相关目标，如ADMET谱、合成可及性和靶标亲和力。此外，我们调查了基于图的分子生成框架，llm引导的蛋白质序列建模和基于扩散的结构预测管道（例如，RFdiffusion, FrameDiff）的进展，这些进展在从头开始的蛋白质工程和构象采样中展示了最先进的性能。生成式人工智能还通过人工智能增强的分子对接（例如DiffDock）、端到端结合亲和预测和量子化学信息的神经电位，催化了基于结构的药物发现的范式转变。我们探索了生成模型与贝叶斯反合成计划、超大化学语料库上的自监督预训练以及精确治疗中组学衍生特征的多模态集成的收敛性。最后，我们讨论了人工智能设计的配体和蛋白质已经发展到临床前和临床验证的转化里程碑，并推测了未来自主分子设计生态系统中生成式人工智能、闭环自动化和量子计算的合成。

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引用次数: 0

Retrospective analysis of glomerular filtration rate estimated using different equations with and without adjustment to individual body surface area 回顾性分析肾小球滤过率估计使用不同的方程式，有和没有调整个人体表面积

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2025-06-30 DOI: 10.1016/j.medidd.2025.100212

Sara Armani , Julia Stingl , Thomas Forst , Josef Höfler , Hannah Wecker , Astrid Trion

The assessment of the influence of renal function on the pharmacokinetics of a new drug is pivotal in many clinical development programs. In clinical trials, renal function is commonly assessed by estimating the glomerular filtration rate (GFR).

Our retrospective analysis compared the assignment of 60 Caucasian volunteers to renal function groups based on their estimated GFR (eGFR). For each volunteer, GFR as measure of renal function was calculated using six commonly used equations (MDRD₂₀₀₆, CKD-EPI_creat2009, CKD-EPI_creat2021, CKD-EPI_cyst2012, CKD-EPI_{creat/cyst2012}, and CKD-EPI_{creat/cyst2021}) with and without adjustment to individual body surface area (BSA).

The resulting distribution of individuals to renal function groups varied across equations. The CKD-EPI_{creat/cyst2012} and CKD-EPI_{creat/cyst2021}, using both creatinine and cystatin C, showed the highest consistency in the renal function group assignment (agreement rate). The agreement rate improved by adjusting with individual BSA (aGFR).

The results support that BSA-adjustment of eGFR may improve the comparability and reproducibility of results of clinical trials where renal function categories are part of the trial design.

评估肾功能对新药药代动力学的影响是许多临床开发项目的关键。在临床试验中，通常通过估算肾小球滤过率（GFR）来评估肾功能。我们的回顾性分析比较了60名高加索志愿者根据他们估计的GFR （eGFR）分配到肾功能组。对于每个志愿者，GFR作为肾功能的测量使用六个常用方程（MDRD2006, CKD-EPIcreat2009, CKD-EPIcreat2021, CKD-EPIcyst2012， CKD-EPIcreat/cyst2012和CKD-EPIcreat/cyst2021）计算，并不调整个人体表面积（BSA）。结果个体到肾功能组的分布在各个方程中各不相同。同时使用肌酐和胱抑素C的CKD-EPIcreat/cyst2012和CKD-EPIcreat/cyst2021在肾功能组分配上显示出最高的一致性（一致性率）。通过调整个体BSA （aGFR）来提高一致性率。结果支持bsa调节eGFR可以提高临床试验结果的可比性和可重复性，其中肾功能分类是试验设计的一部分。

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引用次数: 0

Current demands for standardization of Indian medicinal plants: A critical review 印度药用植物标准化的当前需求：综述

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2025-06-10 DOI: 10.1016/j.medidd.2025.100211

Rishabh Kaundal , Dinesh Kumar

The resurgence of interest in natural products and traditional medicines offers promising avenues for drug discovery. Medicinal plants’ novel chemical and molecular entities dominate current pharmaceutical research. India has mega biodiversity, including medicinal plants that contribute to drug development and health care via traditional practices. Due to the huge demand, a false practice, and quality issues have been observed in the market. Therefore, comprehensive information about standardization methods and processes are the need of hours to maintain quality of raw materials and final products. Thus, the current review insights the significant role of traditional medicines in India, where over 80 % of the population relies on traditional and folklore practices for healthcare needs. This review also summarizes several standardization parameters, including stepwise pharmacognostic studies, WHO guidelines and official pharmacopeia standards. Published literature suggests that research on medicinal plants needs to be encouraged by governments through good policies, regulations, and trade standards of global market. The reviewed information will provide a foundation to develop monographs and quality parameters for Indian traditional drugs and herbal pharmacopoeia.

对天然产物和传统药物兴趣的复苏为药物发现提供了有希望的途径。药用植物的新型化学和分子实体主导着当前的药物研究。印度拥有巨大的生物多样性，包括通过传统做法促进药物开发和医疗保健的药用植物。由于巨大的需求，市场上出现了错误的做法和质量问题。因此，关于标准化方法和过程的综合信息需要小时来保持原材料和最终产品的质量。因此，当前的综述洞察了传统药物在印度的重要作用，在印度，超过80%的人口依靠传统和民间习俗来满足医疗保健需求。本综述还总结了几种标准化参数，包括逐步生药学研究、世卫组织指南和官方药典标准。已发表的文献表明，各国政府需要通过良好的政策、法规和全球市场的贸易标准来鼓励药用植物的研究。这些信息将为制定印度传统药物和草药药典的专著和质量参数提供基础。

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引用次数: 0

Novel indole-based synthetic molecules in cancer treatment: Synthetic strategies and structure-activity relationship 新型吲哚类合成分子在癌症治疗中的应用：合成策略和构效关系

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2025-05-27 DOI: 10.1016/j.medidd.2025.100208

Biplab Debnath , Bikram Nandi , Samiran Paul , Swarup Manna , Arindam Maity , Krishnalekha Bandyopadhyay , Shambo Panda , Shah Alam Khan , Rajarshi Nath , Md Jawaid Akhtar

Indole is one of the naturally occurring nitrogen-containing bicyclic heterocyclic ring systems where benzene and pyrrole rings are fused. It has been demonstrated to exhibit versatile biological activities. The indole scaffold regulates many proteins and genes which play a significant role in cancer development. US Food and Drug Administration (FDA) approved anti-cancer drugs having indole rings in their structure including alectinib, sunitinib, osimertinib, anlotinib, and panobinostat. Several research studies have focused on developing new indole derivatives for the treatment of cancer. Various studies have shown that indole C-3 atom; π-bond in between C-3 and C-2; and nitrogen atom can be substituted with varieties of other structural fragments to overcome the problem of drug resistance and toxicity. The anti-cancer potential of various indole derivatives, their synthetic strategies, and structure–activity relationships (SAR) for the further development and advancement of anticancer therapy. The article also summarizes how different proteins like TRK, VEGFR, EGFR, CDKs, ERK, BRD4, genes like Bcl2, intracellular pathways such as PI3K/AKT/mTOR, enzymes like tubulin and topoisomerase II are inhibited by indole derivatives. Synthetic strategies and SAR will help medicinal chemists to design and develop effective indole derivatives as anticancer agents.

吲哚是一种天然存在的含氮双环杂环体系，由苯和吡咯环融合而成。它已被证明具有多种生物活性。吲哚支架调节了许多在癌症发展中起重要作用的蛋白质和基因。美国食品和药物管理局（FDA）批准了结构中含有吲哚环的抗癌药物，包括阿勒替尼、舒尼替尼、奥西替尼、安洛替尼和帕obinostat。一些研究集中于开发新的吲哚衍生物来治疗癌症。各种研究表明吲哚C-3原子；C-3和C-2之间的π键；氮原子可以被多种其他结构片段取代，以克服耐药和毒性问题。各种吲哚衍生物的抗癌潜力，它们的合成策略和构效关系（SAR）对抗癌治疗的进一步发展和进步。文章还总结了不同的蛋白质如TRK、VEGFR、EGFR、CDKs、ERK、BRD4、基因如Bcl2、细胞内通路如PI3K/AKT/mTOR、酶如微管蛋白和拓扑异构酶II是如何被吲哚衍生物抑制的。合成策略和SAR将帮助药物化学家设计和开发有效的吲哚衍生物作为抗癌药物。

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引用次数: 0