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Unveiling the Anti-cancer Potential of Oxadiazole Derivatives: A Comprehensive Exploration of Structure-Activity Relationships and Chemico-Biological Insights 揭示噁二唑衍生物的抗癌潜力:结构-活性关系和化学-生物学见解的全面探索
IF 2.3 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-09-02 DOI: 10.2174/0115734064329573240823113924
Sai Satyaprakash Mishra, Ajeya Samanta, Abhik Paul, Avik Maji, Tapan Kumar Maity
Background: Oxadiazole derivatives have shown significant potential as anti-cancer agents with low μM potencies. Some examples of drugs in this class include Raltegravir, Zibotentan, Setileuton (MK-0633), Nesapidil, Furamizole, and Tidazosin. The presence of the oxadiazole nucleus in Raltegravir exemplifies its importance in drug development, showcasing how specific structural motifs like oxadiazole can be strategically incorporated into molecules to achieve desired therapeutic effects. A large number of researchers across the globe have already developed and reported many oxadiazoles as potential anti-cancer medicines. Objective: Therefore, we tried to discuss the anti-cancer potentials of oxadiazole derivatives reported between 2019 and 2023. The design strategies, structure-activity relationship (SAR), and protein- inhibitor interactions of potential compounds on different targets have to be identified to help the medicinal chemists design new drug-likeness oxadiazole molecules for anti-cancer therapy. Similarly, the ADMET profiles of potential oxadiazoles using the in silico SWISSADME tool have to be studied. Results: We have highlighted the recently reported most potent oxadiazole derivatives as well as their hybrid compounds. The SAR study revealed that oxadiazole-linked pyridine, indazole, thiadiazine, quinoxaline, thiazolidine, indeno-pyrazole, thiophene, piperidine, benzimidazole, triazole, and sulphonamide showcased promising anti-cancer action. The chemico-biological interactions of potential oxadiazole compounds suggest good interactions with different amino acid residues that make them possible candidates for developing novel and effective anti-cancer therapies. Similarly, the in silico ADMET report suggested favourable physicochemical, pharmacokinetic, and druglikeness properties of potential oxadiazole compounds. Conclusion: Overall, these results will prove to be a helpful and vital tool for medicinal chemists investigating and working with oxadiazoles for anti-cancer action.
背景:噁二唑衍生物作为低μM药效的抗癌药物已显示出巨大的潜力。这类药物包括雷特格韦(Raltegravir)、齐博替坦(Zibotentan)、赛替鲁通(MK-0633)、奈沙吡地尔(Nesapidil)、呋喃唑酮(Furamizole)和替达唑嗪(Tidazosin)。Raltegravir 中的噁二唑核体现了其在药物开发中的重要性,展示了如何将噁二唑等特定结构基团战略性地融入分子中,以达到预期的治疗效果。全球已有大量研究人员开发并报道了许多噁二唑作为潜在的抗癌药物。目的:因此,我们试图讨论 2019 年至 2023 年间报道的噁二唑衍生物的抗癌潜力。必须确定潜在化合物在不同靶点上的设计策略、结构-活性关系(SAR)和蛋白质-抑制剂相互作用,以帮助药物化学家设计新的药物相似性噁二唑分子用于抗癌治疗。同样,还需要使用 SWISSADME 工具研究潜在噁二唑的 ADMET 特征。结果:我们重点介绍了最近报道的最有效的噁二唑衍生物及其混合化合物。SAR 研究表明,与噁二唑连接的吡啶、吲唑、噻二嗪、喹喔啉、噻唑烷、茚并吡唑、噻吩、哌啶、苯并咪唑、三唑和磺酰胺具有良好的抗癌作用。潜在噁二唑化合物的化学生物相互作用表明,它们与不同的氨基酸残基有良好的相互作用,因此可能成为开发新型有效抗癌疗法的候选化合物。同样,硅学 ADMET 报告表明,潜在的噁二唑化合物具有良好的物理化学、药代动力学和药物亲和性。结论总之,这些结果将被证明是药物化学家研究和使用噁二唑抗癌作用的有用和重要的工具。
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引用次数: 0
Exploring the Diverse Therapeutic Applications of 1, 3-Thiazine: A Comprehensive Review 探索 1,3-噻嗪的多种治疗应用:全面回顾
IF 2.3 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-09-02 DOI: 10.2174/0115734064328915240827062052
Neetu Agrawal, Deepika Goyal, Shilpi Pathak
Thiazine, a six-membered heterocycle containing nitrogen and sulfur atoms, is of paramount importance due to its diverse biological functions and broad therapeutic effects. The pharmacological attributes of 1,3-thiazine span a wide range of activities, including antileukemic, antimycobacterial, anti-inflammatory, sedative, hypnotic, anti-influenza, antituberculosis, melanogenesis inhibition, BACE1 inhibition (with anti-Alzheimer's potential), growth promotion, neuroprotective, and anticonvulsant properties. Consequently, novel synthetic methodologies and the design of new 1,3-thiazine derivatives are significantly influenced by recent research findings. This comprehensive review explores both in vivo and in vitro preclinical studies on the biomedical and therapeutic applications of 1,3-thiazine, highlighting its extensive medical relevance. It is anticipated that derivatization strategies for 1,3-thiazine will open new avenues for the development of innovative biological agents. This review aims to engage researchers, stimulating the creation of promising new treatments and preventive measures for various diseases.
噻嗪是一种含有氮原子和硫原子的六元杂环,因其具有多种生物功能和广泛的治疗效果而变得极为重要。1,3-thiazine 的药理特性具有广泛的活性,包括抗白血病、抗霉菌、抗炎、镇静、催眠、抗流感、抗结核、黑色素生成抑制、BACE1 抑制(具有抗阿尔茨海默氏症的潜力)、生长促进、神经保护和抗惊厥特性。因此,新的合成方法和新的 1,3-噻嗪衍生物的设计受到近期研究成果的极大影响。本综述探讨了有关 1,3-噻嗪生物医学和治疗应用的体内和体外临床前研究,强调了其广泛的医学相关性。预计 1,3-噻嗪的衍生化策略将为创新生物制剂的开发开辟新途径。这篇综述旨在吸引研究人员的参与,激励他们为各种疾病开发出有前景的新疗法和预防措施。
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引用次数: 0
Mapping the Landscape of Global Anticancer Organometallics Research: A Systematic Review 绘制全球抗癌有机金属研究图景:系统回顾
IF 2.3 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-09-02 DOI: 10.2174/0115734064317811240815184525
Tanzeel Ur Rehman, Yaser Abdulaziz Alnaam, Misbah Zahid, Jari S. Algethami
Aim: Due to interdisciplinary research, many innovative concepts have been merged that seemed to be impractical. Recently, medicinal organometallic chemistry has made remarkable progress, but the latency of these compounds has not been fully exploited. This systematic review has examined the published literature on anticancer organometallic chemistry across countries, science fields, and organizations involved in organometallics research for cancer. Method: The study data related to anticancer organometallics were searched from Scopus between 2085 and 2022. Biblioshiny and VOS Viewers were used to analyze and visualize patterns in scientific literature derived from Scopus. Results: Publications on organometallic compounds have been found to contribute to, on average, 1.02% per year, accounting for 94.3% of the total scholarly work published in the last two decades since 2003. However, research productivity has been found to be steadily improved, with 81.5% of all publications produced between 2011 and 2022. The countries possessing the highest published work have been found to be China, the UK, and Germany. The leading institutions, the University of Warwick, United Kingdom, and the University of Auckland, New Zealand, have topped the list of organizations with the most publications. Although the use of medicinal organometallics for cancer has become widespread over the last two decennaries, there has been a notable influx of groundbreaking scientific publications in recent years. Conclusion: The findings of this study may enable researchers to envision potential future scenarios for scientific collaborations involving the utilization of organometallics in the treatment of cancer. This study may provide aspiring and current researchers with the necessary tools and knowledge to effectively pursue their research endeavors for scientific collaborations investigating the use of anticancer organometallics in the medicinal field. The areas, such as ruthenium with reactive oxygen species and angiogenesis, represent opportunities for future investigation and innovation.
目的:由于开展了跨学科研究,许多看似不切实际的创新概念得以融合。最近,药用有机金属化学取得了显著进展,但这些化合物的潜能尚未得到充分利用。这篇系统性综述考察了已发表的有关抗癌有机金属化学的文献,涉及癌症有机金属研究的国家、科学领域和组织。方法:在 Scopus 中检索了 2085 年至 2022 年间与抗癌有机金属相关的研究数据。使用 Biblioshiny 和 VOS Viewers 分析和可视化 Scopus 中科学文献的模式。结果:研究发现,自 2003 年以来的二十年间,有关有机金属化合物的论文平均每年占 1.02%,占学术论文总数的 94.3%。不过,研究生产率稳步提高,2011 年至 2022 年间,81.5%的出版物都是在有机金属化合物领域发表的。发表论文最多的国家是中国、英国和德国。英国华威大学和新西兰奥克兰大学是发表论文最多的机构。尽管在过去二十年中,有机金属药剂已广泛用于治疗癌症,但近年来,突破性的科学出版物明显增多。结论本研究的结果可以帮助研究人员展望未来利用有机金属治疗癌症的潜在科学合作方案。本研究可为有抱负的研究人员和目前的研究人员提供必要的工具和知识,以便他们有效地开展研究工作,在医药领域研究抗癌有机金属的使用。钌与活性氧和血管生成等领域代表着未来研究和创新的机遇。
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引用次数: 0
Recent Advances in Anticancer Research of Osmium and Rhodium Complexes 锇和铑配合物抗癌研究的最新进展
IF 2.3 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-09-02 DOI: 10.2174/0115734064327558240826050650
Irena Kostova
: Although platinum and ruthenium complexes have been clinically recognized to be the most efficient metal-based anticancer candidates, applied in a wide range of cancer cell lines, their serious toxic effects and drug resistance require the necessity for new metal antitumor complexes. There is excessive interest in the design of new Pt-group metal complexes, including osmium and rhodium, which have revealed great chemotherapeutic potential. They have demonstrated modes of action that differ from those of the most broadly-used in clinical practice platinum- and rutheniumbased compounds. Os and Rh complexes are equipotent to their platinum and ruthenium analogues. Many Os- and Rh-based complexes with strong antitumor activity and low toxic effects have been developed and recognized for their antineoplastic activity in the last few years. Some of them have exposed different action profiles from the conventional anticancer metal complexes. That is why they might serve as a possible alternative that deserves more investigation, though limited studies on their biological effects have been reported, which is in contrast with the classical isoelectronic Pt and Ru complex compounds. Studies of Os and Rh complexes are currently attracting scientific attention. Recent developments of this interesting class of novel chemotherapeutic agents have been reviewed.
尽管铂和钌络合物已被临床公认为是最有效的金属抗癌候选化合物,可用于多种癌症细胞系,但它们严重的毒性作用和耐药性要求我们必须开发新的金属抗肿瘤络合物。人们对设计新的铂族金属复合物(包括锇和铑)产生了浓厚的兴趣,这些复合物已显示出巨大的化疗潜力。它们的作用模式与临床上最广泛使用的铂基和钌基化合物不同。Os 和 Rh 复合物与铂和钌类似物具有等效性。在过去几年中,许多具有强大抗肿瘤活性和低毒性的 Os 和 Rh 复合物被开发出来,其抗肿瘤活性也得到了认可。其中一些络合物的作用特征与传统的抗癌金属络合物不同。这就是为什么它们可以作为一种可能的替代品,值得进行更多的研究,尽管对其生物效应的研究报道有限,这与经典的等电子铂和钌复合物形成了鲜明对比。Os 和 Rh 复合物的研究目前正引起科学界的关注。本文对这类有趣的新型化疗药物的最新发展进行了综述。
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引用次数: 0
Docking and Molecular Dynamics Studies on Anticancer Activities of Flavonoids as Inhibitors of CDK2 and CDK9 黄酮类化合物作为 CDK2 和 CDK9 抑制剂的抗癌活性的对接和分子动力学研究
IF 2.3 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-08-29 DOI: 10.2174/0115734064314933240812120123
Sony A.S., Xavier Suresh
Background: Flavonoids express a wide range of medicinal properties, our study presented results on the anticancer activity of selected compounds using in silico studies. Objective: In this article, in silico studies were carried out to find promising anticancer lead among selected flavonoid compounds. Methods: Here, we carried out molecular docking and MD simulation for anticancer screening of flavonoid derivatives against CDK2 and CDK9 proteins. Results: Among the compounds under investigation, Flavone and Recoflavone had the lowest binding energy against CDK2/CDK9 targets using docking studies and MD simulations. Conclusion: We can conclude that Flavone and Recoflavone are promising anticancer lead compounds in the development of new anticancer drugs.
背景:黄酮类化合物具有广泛的药用特性,我们的研究利用硅学研究展示了部分化合物的抗癌活性。研究目的本文开展了硅学研究,以从选定的黄酮类化合物中找到有希望的抗癌线索。方法:我们对黄酮类衍生物针对 CDK2 和 CDK9 蛋白的抗癌作用进行了分子对接和 MD 模拟筛选。结果通过对接研究和 MD 模拟,在所研究的化合物中,黄酮和再黄酮与 CDK2/CDK9 靶点的结合能最低。结论我们可以得出结论,黄酮和再黄酮是很有前途的抗癌先导化合物,可用于开发新的抗癌药物。
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引用次数: 0
New Approach as Inhibitor Against Head-Neck Cancer by In silico, DFT, FMOs, Docking, Molecular Dynamic, and ADMET of Euphorbia tirucalli (Pencil Cactus) 通过大戟科植物(铅笔仙人掌)的 In silico、DFT、FMOs、Docking、分子动力学和 ADMET 研究头颈癌抑制剂的新方法
IF 2.3 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-08-28 DOI: 10.2174/0115734064315601240628115330
Md. Abdullah Al Mashud, Ramprosad Devnath, Masuma Anzuman, Mahbuba Iasmin Sumona, Md. Shamim Hossain, Ajoy Kumer, Md. Enamul Kabir Talukder, Md. Mashiar Rahman, Raihan Rahman Imon, Shopnil Akash, Abdelfattah El Moussaoui, Ahmad Mohammad Salamatullah, Mohammed Bourhia
Background: Head and neck cancer (HNC) is on the rise worldwide, endangering lives and straining healthcare systems in both developing and developed nations. Despite the availability of a number of therapy options, the success rate for treating and controlling head and neck cancer remains dismal. To combat the aggressiveness and drug resistance of Epstein-Barr virus (EBV)-positive Head-Neck cancer cells, this study looks into the potential of Euphorbia tirucalli (pencil cactus) leaf extract. Objectives: The goal of this study is to identify prospective therapeutic candidates from the extract of Euphorbia tirucalli (pencil cactus) leaves, which have the ability to inhibit Epstein-Barr virus (EBV)-positive Head-Neck cancer cells. Materials and Methods: The thirteen most important chemical components found in Euphorbia tirucalli (pencil cactus) leaves were analyzed by means of molecular modeling techniques such as Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET), Quantum Mechanics (QM) calculation, Molecular Dynamics (MD) profiling, molecular docking, and molecular dynamics (MD) simulations. Using the Prediction of Activity Spectra for Substances (PASS) model, we assess the potency of these compounds in vitro against an Epstein- Barr virus (EBV)-positive head-neck cancer cell line. Important molecular properties such as chemical potential, electronegativity, hardness, and softness can be determined with the use of quantum chemical calculations employing HOMO-LUMO analysis. These drugs' safety and toxicological characteristics are better understood thanks to assessments of their pharmacokinetics and ADMET. These tests show that there is no risk of hepatotoxicity or cancer in humans and that they are safe to use. In order to verify binding interactions and complex stability, molecular dynamics simulations are used to reveal stable docked complexes. Results: The molecular docking analysis identifies ligands (01), (02), and (10) as strong competitors, with strong binding affinity for the Epstein-Barr virus (EBV)-positive Head-Neck cancer cell line. Not only do the ligands (01), (02), and (10) match the criteria for a potential new inhibitor of head-neck cancer, but they also outperform the present FDA-approved treatment. Conclusion: Taraxerol, euphol, and ephorginol, three phytochemicals isolated from the leaves of the Euphorbia tirucalli (pencil cactus), have been identified as effective anti-cancer agents with the potential to serve as a foundation for novel head-neck cancer therapies, particularly those targeting the Epstein-Barr virus (EBV)-overexpressing subtype of this disease. An effective, individualized treatment plan for head-neck cancer is a long way off, but this study is a major step forward that could change the lives of patients and lessen the global burden of this disease.
背景:头颈部癌症(HNC)在全球范围内呈上升趋势,危及生命,给发展中国家和发达国家的医疗保健系统造成了巨大压力。尽管有多种治疗方法可供选择,但治疗和控制头颈癌的成功率仍然令人沮丧。为了对抗 Epstein-Barr 病毒(EBV)阳性头颈癌细胞的侵袭性和耐药性,本研究探讨了铅笔仙人掌叶提取物(Euphorbia tirucalli)的潜力。研究目的本研究旨在从铅笔仙人掌(Euphorbia tirucalli)叶提取物中找出具有抑制 Epstein-Barr 病毒(EBV)阳性头颈癌细胞能力的潜在候选疗法。材料与方法:通过吸收、分布、代谢、排泄和毒性(ADMET)、量子力学(QM)计算、分子动力学(MD)分析、分子对接和分子动力学(MD)模拟等分子建模技术,分析了笔仙人掌叶中最重要的 13 种化学成分。利用物质活性谱预测(PASS)模型,我们在体外评估了这些化合物对爱泼斯坦巴氏病毒(EBV)阳性头颈癌细胞系的效力。通过量子化学计算和 HOMO-LUMO 分析,可以确定重要的分子特性,如化学势、电负性、硬度和软度。通过对药物动力学和 ADMET 的评估,这些药物的安全性和毒理学特性得到了更好的了解。这些测试表明,这些药物对人体没有肝毒性或致癌风险,可以安全使用。为了验证结合相互作用和复合物的稳定性,我们使用分子动力学模拟来揭示稳定的对接复合物。结果:分子对接分析发现配体(01)、(02)和(10)是强有力的竞争者,它们与 Epstein-Barr 病毒(EBV)阳性头颈癌细胞系有很强的结合亲和力。配体(01)、(02)和(10)不仅符合潜在的头颈癌新抑制剂的标准,而且其疗效优于目前美国食品及药物管理局批准的治疗方法。结论从铅笔仙人掌(Euphorbia tirucalli)叶片中分离出的三种植物化学物质 Taraxerol、euphol 和 ephorginol 已被确认为有效的抗癌剂,有可能成为新型头颈癌疗法的基础,尤其是那些针对这种疾病的 Epstein-Barr 病毒(EBV)表达过高亚型的疗法。针对头颈癌的有效个体化治疗方案还很遥远,但这项研究是向前迈出的重要一步,它可能会改变患者的生活,减轻这种疾病给全球带来的负担。
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引用次数: 0
Platinum Group Metals against Parasites: State of the Art and Future Perspectives 铂族金属对抗寄生虫:技术现状与未来展望
IF 2.3 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-08-26 DOI: 10.2174/0115734064324855240806052735
Jose Manuel Mendez-Arriaga
Background: Globally, parasitic diseases are considered among the neglected diseases. Clinically, several drugs are used in treatment, however due to drug resistance and multidrug resistance and the low investment in new research lines, there has been a failure in the treatment of parasitic illnesses. Objectives: The present mini-review is a comprehensive review of the use of platinum group metals as biological agents. It aims to establish the actual state of the art of these metal elements in the antiparasitic activity-specific area and define the future possibilities of action. Methods: The review comprises more than 100 research works done in this field. The differences between platinum group metals chemistry and their use as metal complexes with biological activity have been discussed. Results: This review highlighted the platinum group metal's potential as an antiparasitic agent for different diseases. Conclusion: The review will be helpful for the researchers involved in targeted drugs for parasitic disease therapy.
背景:在全球范围内,寄生虫病被认为是被忽视的疾病之一。临床上使用多种药物进行治疗,但由于耐药性和多重耐药性以及对新研究方向的投资较少,寄生虫病的治疗一直处于失败状态。目标:本微型综述是对使用铂族金属作为生物制剂的全面回顾。其目的是确定这些金属元素在抗寄生虫活性特定领域的实际技术水平,并确定未来发挥作用的可能性。方法:综述包括该领域的 100 多项研究成果。讨论了铂族金属化学性质与作为具有生物活性的金属配合物之间的差异。结果:这篇综述强调了铂族金属作为抗寄生虫剂治疗不同疾病的潜力。结论这篇综述将对从事寄生虫病靶向药物治疗的研究人员有所帮助。
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引用次数: 0
Synthesis and Evaluation of Antibacterial and Antifungal Activities In vitro and In silico of Novel Morpholinoalkoxychalcones 新型吗啉烷氧基查耳酮的合成及其体外和硅学抗菌和抗真菌活性评价
IF 2.3 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-08-12 DOI: 10.2174/0115734064316022240801093905
Hoang Minh Phan, Tan Thanh Mai, Thinh Nguyen Quang Don, Dat Thanh Do, Khac Minh Thai, Thanh Dao Tran, Phuong Truong, Phuong Nguyen Hoai Huynh
Introduction: Chalcone compounds exhibit diverse bioactivities, attracting significant interest. Morpholine is a heterocycle commonly used in medicinal chemistry. It could enhance the potency, pharmacokinetics, and bioactivities of its compounds. Method: Adding morpholine into the chalcone scaffold could help create new compounds with favorable bioactivities. In this study, a new parallel synthesis procedure has been developed. Using this procedure, 18 novel morpholinoalkoxychalcones have been successfully synthesized. They had chains with morpholine appended on ring A or ring B. All the synthesized compounds were evaluated for the antibacterial and antifungal activities by agar diffusion method on 5 bacteria and 2 fungi strains. Results: The compounds with good inhibition were determined with respect to the MIC values by the agar dilution method. Among the tested compounds, B.21 was found to be the best against S. faecalis, with an MIC value of 0.6 mM. B.43 was found to be the best against A. niger and C. albicans with MIC value of 2.04 mM. Conclusion: The in silico study has revealed two targets to align with the in vitro results. Longer alkyl chains have enhanced the activity, along with the presence of OH, NH2, and halogen groups on both rings A and B. result: We synthesis 18 new morpholinoalkoxychalcones with the chain both on ring A and ring B. All compounds are new based on Scifinder at 10/2023. 3 compounds showed intermediate activity on 5 bacteria strains and 8 compounds showed intermediate activity on 2 fungi strains. The in silico study showed that there were 2 targets suitable with the in vitro results.
简介:查耳酮化合物具有多种生物活性,引起了人们的极大兴趣。吗啉是药物化学中常用的杂环。它可以增强其化合物的药效、药代动力学和生物活性。研究方法在查尔酮支架中加入吗啉有助于创造具有良好生物活性的新化合物。本研究开发了一种新的平行合成程序。利用这一程序,成功合成了 18 种新型吗啉烷氧基查尔酮。通过琼脂扩散法对 5 种细菌和 2 种真菌菌株进行了抗菌和抗真菌活性评估。结果:通过琼脂稀释法测定了具有良好抑菌作用的化合物的 MIC 值。在测试的化合物中,B.21 对粪肠球菌的抑制效果最好,MIC 值为 0.6 mM。B.43 对 A. niger 和 C. albicans 的作用最好,MIC 值为 2.04 mM。结论:硅学研究发现了两个与体外研究结果一致的靶点。较长的烷基链增强了活性,同时 A 环和 B 环上都存在 OH、NH2 和卤素基团:我们合成了 18 种新的吗啉基烷氧基查耳酮,其 A 环和 B 环上都有链。3 个化合物对 5 种细菌菌株显示出中等活性,8 个化合物对 2 种真菌菌株显示出中等活性。硅学研究表明,有 2 个目标与体外结果相吻合。
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引用次数: 0
Exploring Thiophene Derivatives: Synthesis Strategies and Biological Significance 探索噻吩衍生物:合成策略和生物学意义
IF 2.3 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-08-12 DOI: 10.2174/0115734064326879240801043412
Isha Mishra, Vikram Sharma, Nitin Kumar, Gaurav Krishna, Vandana Arora Sethi, Ravi Mittal, Prashant K. Dhakad, Raghav Mishra
Objectives: Thiophene is one of the most important heterocyclic scaffolds with notable pharmacological properties. Thiophene and its derivatives are of particular interest among sulphurcontaining heterocycles because of their similarities to numerous natural and synthetic compounds with identified potential. The purpose of this study is to extensively analyse the synthetic pathways adopted for synthesising thiophene derivatives and investigate their various biological functions. Methods: A comprehensive review of the existing literature was conducted to collect data pertaining to the methods that are employed for the synthesis of thiophene derivatives. A comprehensive search was carried out through relevant databases, including work published in 2024. A variety of synthesis procedures were identified and arranged, encompassing both traditional approaches like the Gewald reaction and contemporary ones like microwave-assisted synthesis and green synthesis. In addition, a comprehensive compilation of in vitro and in vivo studies was conducted to investigate the biological effects of 50 distinct thiophene derivatives. The primary focus of the studies was on various activities such as anti-cancer, anti-inflammatory, antiprotozoal, antibacterial, antioxidant, and antiviral functions. Results: Diverse methodologies have been employed in the synthesis of thiophene derivatives, encompassing both conventional and modern methods. Furthermore, the biological potential of thiophene derivatives was investigated, demonstrating a broad range of actions. Key structural elements necessary for biological activity were clarified by investigations of the structure-activity relationship. Conclusion: The biological potential and flexible synthesis pathways of thiophene derivatives make them attractive candidates for use in medicinal and pharmaceutical chemistry. Understanding the different synthesis methods and biological actions of thiophene derivatives may assist rational design and create novel treatments for a variety of conditions. The potential for these compounds to be further explored and optimised is considerable for the next drug development initiatives.
目的:噻吩是最重要的杂环支架之一,具有显著的药理特性。在含硫杂环中,噻吩及其衍生物尤其令人感兴趣,因为它们与许多具有鉴定潜力的天然和合成化合物相似。本研究的目的是广泛分析合成噻吩衍生物所采用的合成途径,并研究它们的各种生物功能。方法:对现有文献进行了全面审查,以收集与合成噻吩衍生物的方法有关的数据。我们在相关数据库中进行了全面搜索,包括 2024 年发表的作品。确定并整理了各种合成程序,其中既包括格瓦尔德反应等传统方法,也包括微波辅助合成和绿色合成等现代方法。此外,还对体外和体内研究进行了全面汇编,以研究 50 种不同噻吩衍生物的生物效应。研究的主要重点是各种活性,如抗癌、抗炎、抗原虫、抗菌、抗氧化和抗病毒功能。研究结果合成噻吩衍生物的方法多种多样,既有传统方法,也有现代方法。此外,还对噻吩衍生物的生物潜力进行了研究,结果表明噻吩衍生物具有广泛的作用。通过对结构-活性关系的研究,明确了生物活性所需的关键结构元素。结论:噻吩衍生物的生物潜力和灵活的合成途径使其成为药物化学中极具吸引力的候选化合物。了解噻吩衍生物的不同合成方法和生物作用有助于合理设计和创造治疗各种疾病的新方法。进一步探索和优化这些化合物对于下一步的药物开发计划具有相当大的潜力。
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引用次数: 0
Crucial Structural Understanding for Selective HDAC8 Inhibition: Common Pharmacophores, Molecular Docking, Molecular Dynamics, and Zinc Binder Analysis of selective HDAC8 inhibitors. 选择性 HDAC8 抑制的关键结构理解:选择性 HDAC8 抑制剂的常见药理、分子对接、分子动力学和锌粘合剂分析。
IF 1.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-07-19 DOI: 10.2174/0115734064320232240709105228
Kakali Sarkar, Sudhan Debnath, Debanjan Sen, Supratik Kar, Samir Kumar Sil

Background: Overexpression of HDAC8 was observed in various cancers and inhibition of HDAC8 has emerged as a promising therapeutic approach in recent decades.

Objective: This review aims to facilitate the discovery of novel selective HDAC8 inhibitors by analyzing the structural scaffolds of 66 known selective HDAC8 inhibitors, along with their IC50 values against HDAC8 and other HDACs.

Methods: The inhibitors were clustered based on structural symmetry, and common pharmacophores for each cluster were identified using Phase. Molecular docking with all HDACs was performed to determine binding affinity and crucial interacting residues for HDAC8 inhibition. Representative inhibitors from each cluster were subjected to molecular dynamics simulation to analyze RMSD, RMSF, active site amino acid residues, and crucial interacting residues responsible for HDAC8 inhibition. The study reviewed the active site amino acid information, active site cavities of all HDACs, and the basic structure of Zn2+ binding groups.

Results: Common pharmacophores identified included AADHR_1, AADDR_1, ADDR_1, ADHHR_1, and AADRR_1. Molecular docking analysis revealed crucial interacting residues: HIS- 142, GLY-151, HIS-143, PHE-152, PHE-20 in the main pocket, and ARG-37, TYR-100, TYR-111, TYR-306 in the secondary pocket. The RMSD of protein and RMSF of active site amino acid residues for stable protein-ligand complexes were less than 2.4 Å and 1.0 Å, respectively, as identified from MD trajectories. The range of Molecular Mechanics Generalized Born Surface Area (MMGBSA) ΔG predicted from MD trajectories was between -15.8379 Å and -61.5017 Å kcal/mol.

Conclusion: These findings may expedite the rapid discovery of selective HDAC8 inhibitors subject to experimental evaluation.

背景:近几十年来,抑制 HDAC8 已成为一种有前景的治疗方法:本综述旨在通过分析66种已知选择性HDAC8抑制剂的结构支架及其对HDAC8和其他HDACs的IC50值,促进新型选择性HDAC8抑制剂的发现:方法:根据结构对称性对抑制剂进行聚类,并使用相位法确定每个聚类的共同药理作用。与所有 HDACs 进行分子对接,以确定结合亲和力和抑制 HDAC8 的关键相互作用残基。对每个群组中具有代表性的抑制剂进行了分子动力学模拟,以分析RMSD、RMSF、活性位点氨基酸残基以及抑制HDAC8的关键相互作用残基。研究回顾了所有 HDAC 的活性位点氨基酸信息、活性位点空腔以及 Zn2+ 结合基团的基本结构:结果:发现的常见药效基团包括 AADHR_1、AADDR_1、ADDR_1、ADHHR_1 和 AADRR_1。分子对接分析发现了关键的相互作用残基:主口袋中的 HIS- 142、GLY-151、HIS-143、PHE-152 和 PHE-20,以及次口袋中的 ARG-37、TYR-100、TYR-111 和 TYR-306。根据 MD 轨迹确定的稳定蛋白质配体的蛋白质 RMSD 和活性位点氨基酸残基 RMSF 分别小于 2.4 Å 和 1.0 Å。根据 MD 轨迹预测的分子力学广义玻恩表面积 (MMGBSA) ΔG 范围在 -15.8379 Å 和 -61.5017 Å kcal/mol 之间:结论:这些发现可能会加快选择性 HDAC8 抑制剂的快速发现,并对其进行实验评估。
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Medicinal Chemistry
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