唐松草属植物中生物碱类化学成分和药理作用的研究进展

毛茛科唐松草属植物由于具有较高的药用价值,在我国广泛应用。唐松草属植物的生物碱属于异喹啉类,包括生物碱单聚物如简单异喹啉类、苄基异喹啉类、阿朴菲类、原小檗碱类、吗啡烷类、异帕威类等;此外还存在大量的二聚生物碱,主要类型有双苄基异喹啉类、阿朴菲–苄基异喹啉类、原小檗碱–苄基异喹啉类、阿朴菲–原小檗碱类等;具有抗肿瘤、抗寄生虫、抗血小板聚集、抗矽肺、抗病毒等药理作用。主要对唐松草属植物中生物碱类化学成分和药理作用的研究进展进行综述,为该属植物资源的开发利用提供参考。     

苄基异喹啉类生物碱药理作用及机制的研究进展

苄基异喹啉类生物碱是自然界中很重要的一类生物碱,数量多,结构类型复杂。药理学研究已经证实苄基异喹啉类生物碱具有抗肿瘤、抗炎、抗病毒以及抗血小板凝集、抗心律失常和抗高血压等心血管疾病的多种药理活性,同时该类生物碱还显示出抗菌、肌肉松弛、降血糖、机体自身免疫调节以及中枢神经系统方面的药理作用,临床应用表明了确实的疗效。本文对该类生物碱丰富的药理作用及机制研究进行了综述。     

四氢异喹啉类生物碱的生物活性多样性及其作用机制

四氢异喹啉类生物碱在自然界中分布广泛, 有些药物在临床上已广泛应用。随着对四氢异喹啉类生物碱研究的深入, 越来越多新的生物活性、新的作用机制和靶点被发现和揭示, 此类生物碱生物活性的多样性受到人们广泛关注。本文综述了近五年来四氢异喹啉类化合物在抗肿瘤、抗菌、抗病毒、抗炎、抗凝血、支气管扩张及中枢神经系统作用等方面的活性及机制研究的新进展, 旨在为四氢异喹啉类生物碱的活性研究提供思路和启示, 为寻找先导化合物、合理设计药物分子提供依据。     

1-(4-烃氧基)苄基四氢异喹啉类化合物及相关化合物的合成与生物活性

以有心血管活性的异喹啉生物碱为先导物,设计合成了15个3,4-二氢(II_1,2)和1,2,3,4-四氢-(4-烃氧基)苄基四氢异喹啉化合物(II_3～15)。药理实验表明:大部分化合物有舒张血管条作用,其中化合物II₉对低钾诱导的血管收缩有较强的抑制作用,而对高钾诱导的血管收缩无作用,对硝酸乌头碱诱发的大鼠室性心律失常有明显保护作用。     

1—（4—酰氧基苄基）四氢异喹啉类化合物的合成

以具心血管活性的异喹啉生物碱为先导物，设计合成了１０个未见文献报道的１－（４－酰氧基苄基）四氢异喹啉类化合物，结构经元素分析、红外光谱、核磁共振谱和质谱确证。     

1—（4—胺乙酰胺基）苄基四氢异喹啉类化合物的合成及其心血管活性

研究发现某些异喹啉类化合物具有较好的心血管活性，Ｎ胺乙酰基取代的苄基四氢异喹啉化合物对二氢吡啶（ＤＨＰ）受体有较好的亲和力〔１〕．据报道〔２〕化合物１（２乙胺基乙酰胺基３，４二甲氧基）苄基异喹啉具有较强的抗心律失常作用，毒性远低于利多卡因．...     

合成苄基二氢异喹啉类化合物时一特例反应

<正> 苄基二氢异喹啉类化合物是合成具有特殊药理活性的阿朴菲类、吗啡二烯酮等生物碱的重要中间体,且本身也有很强的药理活性,因此,我们经Bischler-Napieraski法合成一系列的苄基二氢异喹啉类化合物,其中发现一特列反应即:(±)N-(3,4-甲二氧基苯乙基)-α-甲氧基-邻-氯苯乙酰胺(Ⅰ)在成环时α-甲氧基氧化成羰基氧。反应后得到产物Ⅱ,未得到预计产物Ⅱ’.反应式如下:     

取代苄基/萘甲基异喹啉类及有关季铵衍生物的合成与生物活性

以具心血管活性的异喹啉类生物碱为先导物,结合某些钾通道阻滞剂的结构特征,设计合成了28个3,4-二氢(I_1～4)和1,2,3,4-四氢苄基/萘甲基异喹啉化合物(II_1～18)及有关季铵衍生物(I_5,6和II_19～22)。药理试验表明:除化合物I₄有一定升压作用外,大多化合物有不同程度的降压和减慢心率活性,其中化合物II1的降压活性最强。分析定量构效关系发现:化合物母核氮原子电荷愈大(即其绝对值愈小),降压作用愈强;反之,减慢心率作用愈强。异喹啉母核氮原子电荷可能为影响作用于血管或心脏组织的重要因素之一。     

RAW 264.7细胞炎症模型优化及异喹啉类生物碱抗炎活性研究

目的 对RAW 264.7细胞炎症模型进行优化,并考察异喹啉类生物碱的抗炎活性。方法 采用内毒素脂多糖（LPS）诱导RAW264.7细胞炎症反应,以细胞上清液中炎症因子分泌水平为指标,优化LPS诱导浓度、时间及阳性药地塞米松（DEX）孵育时间,并考察异喹啉类生物碱的抗炎活性。结果 RAW 264.7细胞上清液中肿瘤坏死因子-α（TNF-α）分泌水平随LPS诱导浓度、时间增加而升高,但当LPS质量浓度超过100 ng/mL、诱导时间超过12 h后,TNF-α分泌水平趋于平缓;LPS为20 ng/mL、诱导12 h的TNF-α分泌水平明显升高。DEX对TNF-α分泌抑制作用随孵育时间延长而增强,但孵育4 h后,TNF-α分泌抑制作用趋于平缓。异喹啉类生物碱呈现不同程度TNF-α分泌抑制作用,其抑制活性与其季胺型母核结构及R基团烷氧基取代等密切相关。结论 LPS为20 ng/mL、诱导12 h能较好诱导RAW 264.7细胞炎症反应;异喹啉类生物碱的TNF-α分泌抑制作用与其季胺型母核结构、R基团取代等密切相关。     

N—取代四氢苄基异喹啉类化合物的合成

Ｎ┐取代四氢苄基异喹啉类化合物的合成马玉卓１）刘鹰翔（鱼它滨化学药业总公司研究所，汕头５１５０４１）容士宏张新华（沈阳药科大学制药系，沈阳１１００１５）近来国内文献曾报道一系列苄基异喹啉衍生物或类似物对心血管系统具有多方面的药理作用［１～３］。但是通...     

1,3,7,9-四甲基尿酸的研究进展

摘 要 1,3,7,9 四甲基尿酸是天然存在的嘌呤类生物碱,主要存在于苦茶中,具有抗抑郁、镇静催眠和抗炎镇痛等药理作用。本文结合最近十几年的文献,对1,3,7,9 四甲基尿酸的资源、制备、检测方法及药理作用等进行综述,并探讨了1,3,7,9 四甲基尿酸的应用前景。     

马齿苋生物碱的研究进展

马齿苋是一种药食同源的植物,其主要含有生物碱、黄酮、萜类、多糖等成分,因其生物碱结构类型多样,且具有较好的药理活性,近年来引起了广泛关注。主要针对马齿苋中生物碱类化合物的结构类型、药理活性、质量评价及体内代谢研究进展进行归纳总结,为马齿苋的开发利用及进一步研究提供参考。     

Therapeutic potential of naringin: an overview

Context: Naringin is a natural flavanone glycoside that is found in the Chinese herbal medicines and citrus fruits. Studies have demonstrated that naringin possesses numerous biological and pharmacological properties, but few reviews of these studies have been performed.

Objective: The present review gathers the fragmented information available in the literature describing the extraction of naringin, its pharmacology and its controlled release formulations. Current research progress and the therapeutic potential of naringin are also discussed.

Methods: A literature survey for relevant information regarding the biological and pharmacological properties of naringin was conducted using Pubmed, Sciencedirect, MEDLINE, Springerlink and Google Scholar electronic databases from the year 2007–2015.

Results: Naringin modulates signalling pathways and interacts with signalling molecules and thus has a wide range of pharmacological activities, including anti-inflammatory, anti-cancer activities, as well as effects on bone regeneration, metabolic syndrome, oxidative stress, genetic damage and central nervous system (CNS) diseases. Information was gathered that showed the extraction of naringin can be improved using several modifications. There has been some progress in the development of controlled release formulations of naringin.

Conclusion: Naringin is a promising candidate for further in vivo studies and clinical use. More detailed studies regarding its mechanism of action are required.     

石斛的化学成分及药理作用研究进展

目的 综述石斛化学成分及药理作用的研究进展,为石斛的合理开发和临床应用提供理论参考.方法 分别以"石斛""Dendrobium"等为关键词在中国知网、PubMed等数据库中查询近十年关于石斛化学成分、药理作用及炮制工艺的文献,并选取具有代表性的进行整理综述.结果 石斛的化学成分复杂,主要包括多糖类、生物碱类、黄酮类、菲...     

New substituted benzimidazole derivatives: a patent review (2013 – 2014)

Introduction: The benzimidazole nucleus is found in a variety of naturally occurring compounds and is of significant importance in medicinal chemistry. Owing to its conspicuous pharmacological properties, benzimidazoles have become an important pharmacophore and sub-structure in drug design and have been screened for a wide range of biological activities.

Areas covered: Areas covered in this paper include a review of the biological effects, mechanisms and synthesis of benzimidazole derivatives in the past 2 years based on patents. The patent databases Scifinder and esp@cenet were used to locate patent applications that were published between 2013 to present. Information from articles published is also included.

Expert opinion: Benzimidazole derivatives are remarkably effective compounds to many diseases and may have the potential to be the first effective therapy against Ebola virus. Therefore, it is of great importance to develop specific design software and sustainable industrial synthetic routes for the development of effective and clinically relevant benzimidazole compounds.     

Salvadora persica L.: Toothbrush tree with health benefits and industrial applications – An updated evidence-based review

Salvadora persica L. is also known as Arak (in Arabic) and Peelu (in Urdu). Its frequent use as a toothbrush (miswak) is highly recommended by Prophet Muhammad. With a long history in folk medicine for centuries, S. persica was used in oral hygiene, food, cosmetics, fuel, and even as a medicine. Previous phytochemical investigation of its different parts afforded different classes of secondary metabolites such as flavonoids, glycosides, sterols, terpenes, carbohydrates and alkaloids. Organic sulfur-containing compounds and elemental sulfur are also present. In addition, there is a huge research on its biological potentials and industrial applications. Many pharmacological activities were reported experimentally, including antimicrobial, antioxidant, analgesic, anthelmintic, anti-inflammatory, antiulcer, sedative, anticonvulsant, anti-osteoporosis, antidiabetic, hypo-lipidemic, in addition to wound-healing, antidepressant and antitumor activities. Recently, a possible activity against COVID-19 protease was documented by molecular docking. This review tries to provide a recent detailed documentation of folk and modern uses of S. persica, focusing on the possible relations between its chemical constituents, pharmacological properties, and industrial applications. Moreover, a brief about recent analytical and validation methods for the major antimicrobial component is reported.     

Pyrazine derivatives: a patent review (2008 – present)

Introduction: Pyrazines derivatives are well-known and important two-nitrogen-containing six-membered ring aromatic heterocyclic compounds and can carry substituents at one or more of the four ring carbon atoms. Pyrazines are a class of compounds that occur in nature and various methods have been worked out for their synthesis. A large number of pyrazine derivatives have been found to possess diverse pharmacological properties, which has caused an increasing interest by researchers in this core.

Area covered: This review provides a comprehensive review of the pyrazines derivatives patented between the years 2008 to 2012 as potential active compounds. The patent databases SciFinder and esp@cenet were used to locate patent applications that were published between 2008 to present. Information from articles published was also included.

Expert opinion: The diversity of pyrazines derivatives found in organisms in nature with different applications began to arouse the interest of research in this nucleus. The pyrazines derivatives have numerous prominent pharmacological effects, such as antibacterial, antifungal, antimycobacterial, anti-inflammatory, analgesic, anticancer for different types, antidiabetic, treatment for arteriosclerosis, antiviral. It's the time to conduct further studies aimed at rationalizing the biological activities found in order to develop more effective and clinically interesting compounds.     

Salvadora persica L.: Toothbrush tree with health benefits and industrial applications – An updated evidence-based review

Salvadora persica L. is also known as Arak (in Arabic) and Peelu (in Urdu). Its frequent use as a toothbrush (miswak) is highly recommended by Prophet Muhammad. With a long history in folk medicine for centuries, S. persica was used in oral hygiene, food, cosmetics, fuel, and even as a medicine. Previous phytochemical investigation of its different parts afforded different classes of secondary metabolites such as flavonoids, glycosides, sterols, terpenes, carbohydrates and alkaloids. Organic sulfur-containing compounds and elemental sulfur are also present. In addition, there is a huge research on its biological potentials and industrial applications. Many pharmacological activities were reported experimentally, including antimicrobial, antioxidant, analgesic, anthelmintic, anti-inflammatory, antiulcer, sedative, anticonvulsant, anti-osteoporosis, antidiabetic, hypo-lipidemic, in addition to wound-healing, antidepressant and antitumor activities. Recently, a possible activity against COVID-19 protease was documented by molecular docking. This review tries to provide a recent detailed documentation of folk and modern uses of S. persica, focusing on the possible relations between its chemical constituents, pharmacological properties, and industrial applications. Moreover, a brief about recent analytical and validation methods for the major antimicrobial component is reported.     

Shikonin and its derivatives: a patent review

Introduction: Shikonin and its derivatives are the main components of red pigment extracts from Lithospermum erythrorhizon, whose medicinal properties have been confirmed for a long history, and have aroused great interest as the hallmark molecules responsible for their significant biological activities, especially for their striking anticancer effects.

Areas covered: Areas covered in this paper include a review of the total synthesis, biological effects and mechanisms of shikonin and its derivatives for their anticancer activities in the past decade, basing on literature and patents. The current state and problems are also discussed.

Expert opinion: At present, screening for anticancer shikonin derivatives is based on cellular level to find compounds with stronger cytotoxicity. Though several compounds have been discovered with striking cytotoxicity in vitro, however, no selectivity was observed and undoubtedly, the further outcomes have been disappointing because of their great damage to normal cells. Meanwhile, the presumed mechanisms of action are also established in terms of their cytotoxicity. From a pharmacological point of view, most of the shikonin derivatives are at an early stage of their development, and thus it is difficult to determine the exact effectiveness in cancer treatment. With research in this field going deeper, it can be expected that, despite the difficulties, shikonin derivatives as potential anticancer agents will soon follow.     

石斛属中药生物碱抗肿瘤药理作用及机制研究进展

石斛属 Dendrobium Sw. 中药生物碱类成分结构新颖,药理作用丰富多样,特别是在抗肿瘤方面的表现尤为突出,多种石斛属中药生物碱已被证实对肺癌、胃癌、肝癌、乳腺癌、结肠癌、宫颈癌等有显著的抗肿瘤活性,显示出新药开发潜力。但目前对其抗肿瘤药理作用及机制的系统分析仍然不足,使得在理解和应用石斛属生物碱的过程中存在一定的盲点和局限性。梳理并深入探讨石斛属中药生物碱成分对不同癌症的药理作用,对其常规的抗肿瘤作用机制如诱导肿瘤细胞凋亡、增强机体免疫功能、抑制肿瘤细胞的迁移、细胞周期调控进行解析,并揭示其可能的作用靶点,为其在抗肿瘤研究领域的深入探索和开发利用提供有力的参考和依据。