小檗碱的结构修饰及其药理学活性研究进展

小檗碱类化合物是异喹啉生物碱中一个重要组成部分,其生理功能广泛,对其构效关系的研究较多,具有很大的结构改造和修饰的空间。本文按其主要药理学活性,对小檗碱及其衍生物的结构修饰进展作一综述。     

小檗碱的结构改造及其药理活性的研究进展

小檗碱是从中草药黄连等植物中提取并分离得到的一类异喹啉类生物碱。近年来合成了大量小檗碱衍生物,并且发现了广泛的生理功能,其潜在的结构改造和开发应用价值很大。笔者对这些文献进行了较为系统的分析和整理,通过小檗碱不同位点的衍生物所展现的丰富的药理活性,为以小檗碱作为先导物进行的结构改造及创新药物提供了比较系统的信息。     

小檗碱的抗病原生物作用研究进展

小檗碱又名黄连素,具有非常广泛的药理活性,但其准确的作用靶点至今不清.本文主要综述其抗病毒作用、抗细菌作用、抗真菌作用及其作用的构效关系和分子机制,对揭示生命现象的本质,发现新药靶点具有重要意义,也为小檗碱的结构优化改造和应用研究提供新的线索.     

姜黄素衍生物生物活性的研究进展

目的阐述姜黄素及其衍生物的最新研究进展。方法根据关于姜黄素及其衍生物的研究开发现状的多篇相关文献,对姜黄素的苯环和中间连接链的结构改造特点进行整理和归纳。结果与结论大多数姜黄素衍生物的生物活性都有所提高。另外还总结了一部分化合物的构效关系。     

单酚类抗氧化剂及其衍生物的抗肿瘤作用及机制

目的 筛选单酚类抗氧化剂衍生物以发现新型抗肿瘤药物。方法 参考国内外相关文献,对单酚类抗氧化剂及其衍生物的的抗肿瘤作用的机制和构效关系进行综述。结果 结构修饰后的单酚类衍生物比单酚抗氧化剂的抗肿瘤活性及稳定性明显提高。结论 通过对抗氧化活性较高的单酚类衍生物构效关系进行研究,将有可能为临床提供更多的安全、有效药物。     

小檗碱衍生物的活性研究进展

小檗碱是一种来源于植物的天然药物,其在医药领域内具有广泛的应用价值。本文综述了近年来小檗碱衍生物的活性研究进展,旨在能为以天然产物小檗碱为核心的结构改造上提供一些有益的帮助。     

DNA拓扑异构酶Ⅰ抑制药--抗肿瘤药喜树碱类衍生物的研究进展

目的：DNA拓扑异构酶Ⅰ是生物体内及其重要的细胞核内酶，参与DNA复制、转录、重组和修复等所有关键的核内过程。该酶已成为重要的抗肿瘤药物研究新靶点。讨论了该酶特异性抑制剂喜树碱类衍生物研究进展。方法：以近年来国内外发表的论文为基础，介绍拓扑异构酶Ⅰ结构、功能研究的最新成果。系统总结了喜树碱类衍生物的构效关系，依据构效关系介绍了最新的结构修饰而得衍生物。结果与结论：将为新型DNA拓扑异构酶Ⅰ抑制剂的合理药物设计打下一定的基础。     

DDPH 衍生物α1-受体拮抗活性三维定量构效关系的研究

目的和方法应用计算机模拟Apex3D软件研究DDPH及其衍生物拮抗α1受体活性的三维定量构效关系。结果结果表明芳氧烷胺结构中芳环邻、对位取代对生物活性有重要影响。结论我们所构建的药效团和三维定量构效关系方程不仅能帮助理解药物与受体的相互作用,而且为设计活性更好的新化合物提供参考。     

近年来中草药化学成分及其衍生物和类似物的合成研究

近十年来我国中草药化学成分及其衍生物和类似物的化学合成研究,已取得了极大的进展。一些中草药有效成分人工合成成功,有的已应用于临床。许多中草药有效成分被选为先导化合物,有目的地进行结构改造,合成了大量新化合物;从构效关系研究中,发现了不少生物活性优于母体的化合物,有的已开发成为新药。这些研究使我国天然药物化学的研究达到了一个新的水平。本文就近十年来的研究进展按化学结构分类综述如下。     

环孢素的生物学活性及其衍生物的研究进展

自环孢素作为高效免疫抑制剂应用于临床以来,在其免疫抑制作用机制和构效关系、抗HIV、逆转肿瘤多药耐药及抗炎等生物活性方面进行了深入的研究、在环孢菌素同系物及其衍生物的研发方面也取得许多进展.本文综述了这些方面的研究和进展.     

Pharmacological effects of berberine and its derivatives: a patent update

Introduction: A number of plant-derived agents are used in many therapeutic areas. Berberine, an important protoberberine alkaloid, is present in a number of medicinal plants that have been widely used in traditional Chinese medicine for hundreds of years. Modern research has shown that berberine and its derivatives display several pharmacological effects through various mechanisms.

Areas covered: This review discusses recent and mostly Chinese patents that report the synthesis of berberine, berberine derivatives and berberine salts, and methods of preparation for formulations (traditional Chinese medicine) containing herbal components rich in berberine, along with their applications. The review covers several therapeutic effects of berberine, its derivatives and pharmaceutical formulations against cancer, obesity, diabetes, inflammation, atherosclerosis, Alzheimer’s disease, rheumatoid arthritis and cardiovascular diseases. In addition, the mechanisms underlying the pharmacological effects are discussed.

Expert opinion: Modification of the functional groups of berberine has a significant effect on the pharmacological activity. However, studies on altering the atoms and size of the berberine skeleton are rare. Thus, it may be beneficial to initiate a drug development program focused on inserting heterocyclic rings of different sizes into berberine. Furthermore, structural modification to improve the safety, efficacy and selectivity is necessary to promote the use of berberine-based drugs in clinical settings.     

Advances in structural modifications and biological activities of berberine: an active compound in traditional Chinese medicine

Berberine is an isoquinoline alkaloid isolated from Chinese herbs such as Coptidis Rhizome. This paper is a systematic review of the structural modifications of berberine for different biological activities such as antitumor, antimicrobial, anti-Alzheimer's disease, antihyperglycemic, anti-inflammatory and antimalaria. The current review would provide some useful information for further studies on structural modification of berberine for discovering new drug leads.     

喜树碱结构修饰与构效关系研究进展

喜树碱是从喜树提取物中分离出的能够抗细胞增殖的天然生物碱。由于其溶解性低、稳定性差和显著的不良反应限制了其临床应用,所以在过去的十余年里合成了许多喜树碱衍生物。通过引入极性基团、靶向剂或药效团拼合、前药等在喹啉环、5位和20位进行结构修饰,其中大多数与喜树碱相比显示出更强的效力,对不同的肿瘤细胞具有活性,其中许多对多药耐药肿瘤细胞具有活性。综述了近年来47个新的喜树碱衍生物的合成方法和生物活性,并总结了构效关系,发现在喹啉环和内酯环的羟基上修饰通常可以增强体外抗肿瘤活性,药物递送系统、计算机高通量筛选等新技术的应用为改善喜树碱的溶解性、稳定性,寻找活性较好的先导化合物拓展了新思路。     

水飞蓟宾类黄酮木质素衍生物的研究进展

水飞蓟是多国药典收载的天然药物,具有抗氧化、抗纤维化、抗炎、免疫调节以及肝细胞再生作用,临床用于治疗肝炎、脂肪肝、肝硬化、缺血性损伤、辐射损伤等。近期随着水飞蓟宾以抗肿瘤新药进入Ⅱ期临床试验,对其衍生物、构效关系以及抗氧化机制等的研究进入加速阶段。本文综述了近年来水飞蓟宾和脱氢水飞蓟宾的近百种衍生物及其活性研究结果 ,并对该类黄酮木质素类化合物今后的发展和设计研究状况做一概述。     

Dronedarone as a new treatment option for atrial fibrillation patients: pharmacokinetics,pharmacodynamics and clinical practice

Importance of the field: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting 1 – 2% of the population. Despite several developments in antithrombotic, antiatherosclerotic and device-based cardiac therapies, few noteworthy antiarrhythmic drugs have been developed.

Areas covered in this review: Dronedarone, a modified analogue of amiodarone, has the pharmacological ability of blocking multiple ion channels. This overview summarizes the pharmacokinetic and pharmacodynamic properties of dronedarone, evaluates its potential application to daily clinical cardiology practice according to the evidence provided by clinical trials, and provides a future clinical perspective for the use of this drug.

What the reader will gain: The readers will gain an understanding of the findings of recent trials performed with dronedarone, which will provide important information for this relatively new antiarrhythmic drug, used for the treatment of atrial fibrillation.

Take home message: Dronedarone provides a reasonable efficacy and safety profile. Recent clinical trials indicate that dronedarone may support maintenance of sinus rhythm, decrease hospitalizations and reduce healthcare costs even in AF patients with structural heart disease but without severe or unstable cardiac failure.     

雷公藤内酯醇结构修饰和构效关系研究进展

雷公藤中的雷公藤内酯醇具有抗肿瘤、免疫抑制等多种生物活性,但是副作用大等特点限制了临床的使用。为了获得高效低毒的雷公藤内酯醇衍生物,对其结构进行了改造。近5年来对雷公藤内酯醇的结构改造又有了新进展,包括对其14位羟基、不饱和五元内酯环、B环、13位异丙基和10位甲基的结构改造,得到一系列衍生物。其中对14位羟基进行前药设计,从而降低了雷公藤内酯醇的毒性,14位羟基改造为α-羟基衍生物后发现了与雷公藤内酯醇活性相当的衍生物。综述了近5年来对雷公藤内酯醇的结构改造及构效关系研究进展。     

Prospects for the creation of new antiviral drugs based on glycyrrhizic acid and its derivatives (a review)

The review is devoted to the problem of creating new antiviral drugs based on glycyrrhizic acid (GA), the major triterpene glycoside extracted from roots of common and Ural licorice (Glycyrrhiza glabra L. and G. uralensis Fisher, respectively). Published data on the natural GA sources, antiviral activity of GA and its derivatives, clinical applications of GA-based drugs, and the properties of GA-containing biologically active nutrient additives are summarized. Possible mechanisms of the antiviral activity of GA and its derivatives are examined. It is shown that chemical modification of GA is a promising way of designing new highly active antiviral drugs for the prophylaxis and treatment of HIV, hepatitis B and C, corona-virus, and herpes simplex virus infections.     

Recent advances on structural modifications of benzothiazoles and their conjugate systems as potential chemotherapeutics

INTRODUCTION: Benzothiazole scaffold comprises a bicyclic ring system and is known to exhibit a wide range of biological properties including antimicrobial and anticancer activities. Benzothiazole derivatives have long been therapeutically used for the treatment of various diseases. However, in recent years, 2-arylbenzothiazoles have emerged as an important pharmacophore in the development of antitumor agents. The promising biological profile and synthetic accessibility have been attractive in the design and development of new benzothiazoles and their conjugate systems as potential chemotherapeutics. AREAS COVERED: This review mainly focuses on the structural modifications of benzothiazole scaffold, development of various series of benzothiazoles and their conjugates as new antitumor agents. Furthermore, heterocyclic derivatives bearing benzothiazole moiety and their in vitro as well as in vivo screening, structure-activity relationships (SAR), mechanism, pharmacokinetics, clinical use and their future therapeutic applications are discussed here. EXPERT OPINION: A large number of benzothiazole derivatives discussed here possess potent anticancer activity and can be further developed as drug candidates. Benzothiazole conjugates could also display synergistic effect and still there is a need to use the drug combinations permitting lower dose and development of new generation of drugs. Despite encouraging results that have been observed for their response to tumor in clinical studies, full characterization of their toxicity is further required for their clinical usage as safe drugs for the treatment of cancer. We believe that this review gives a better understanding and scope for future drug design and development of benzothiazole-based compounds to implicate their use in cancer chemotherapy.     

Lessons from black pepper: piperine and derivatives thereof

Introduction: Piperine is a simple and pungent alkaloid found in the seeds of black pepper (Piper nigrum). Following its isolation and full characterization, the biological properties of piperine have been extensively studied, and piperine-like derivatives have shown an interesting range of pharmacological activities. In this context, significant advances have been made in the discovery of new chemical entities based on the piperine scaffold endowed with therapeutic potential.

Areas covered: The aim of this review is to provide a thorough inquiry on the therapeutic potential of piperine and related derivatives. It provides an overview of recent developments in patented processes and applications thereof between 2000 and 2015.

Expert opinion: Cumulative evidence shows that piperine is currently paving its way to become a privileged scaffold for the development of bioactive compounds with therapeutic application in multiple human diseases. In particular, piperine derivatives were shown to modulate the activity of several targets related to neurological disorders, including epilepsy, Parkinson’s disease, depression and pain related disorders. Moreover, the efflux pump inhibitory ability of piperine and its analogues tackles important drug resistance mechanisms and may improve the clinical efficacy of antibiotic and anticancer drugs. Although the use of piperine as a scaffold for bioactive compounds is still in its early stages, the continuous exploration of this structure may lead to remarkable advances in drug discovery programs.