白桦酸及其衍生物的研究进展

对白桦酸衍生物的构效关系及其中的YK-FH312、RPR103611和IC9564等的作用机制及活性进行述评。天然产物白桦酸是有抗HIV和抗肿瘤活性，且具有新型结构和新型作用机制的化合物，其天然来源广泛，半合成方法成熟，是寻找抗HIV和抗肿瘤药物的优秀的先导物。通过对白桦酸的结构修饰，大量白桦酸衍生物已被合成。     

白桦醇与白桦酸的结构修饰与抗肿瘤活性研究进展

目的综述白桦醇和白桦酸的结构改造及其抗肿瘤活性研究进展。方法通过查阅40余篇相关文献,对白桦醇和白桦酸的抗肿瘤活性与这两个化合物的结构改造及其抗肿瘤活性方面进行归纳总结。结果白桦醇、白桦酸以及它们的衍生物在治疗癌症方面显示了巨大的潜力,在这两个化合物的结构改造中,均以引入杂原子和不饱和基团对其抗肿瘤活性的提高作用最明显。结果白桦醇与白桦酸及其结构改造仍是抗肿瘤药物的研究热点,值得进一步研究开发。     

白桦酸类化合物的研究进展

白桦酸类化合物是一类可以从多种植物中分离得到的天然产物，包括白桦酸、23-羟基白桦酸、白桦素及其衍生物等，是一类结构及作用机制相对新颖、具有抗HIV-1和抗肿增活性的天然化合物。对这类化合物的结构修饰和改造，目前已经获得大量具有良好生物活性的衍生物。现对这方面的研究进展进行综述。     

白桦酸类化合物抗肿瘤活性的研究进展

癌症一直以来是威胁人类健康的头号杀手。然而,目前临床中使用的大部分抗肿瘤药物缺少选择性,在对肿瘤细胞发挥作用的同时,也会对正常细胞产生毒性。因此人们希望能从天然植物中分离得到理想的抗肿瘤先导化合物。白桦酸是天然的羽扇豆烷型三萜类化合物,1995年,人们首次     

睡菜中的抗炎成分

睡菜(Menyanthes trifoliata L.)是瑞典民间用于治疗肾炎的一种传统药用植物,其粗提物对体外前列腺素合成具明显的抑制作用。从该植物的根茎中分得8个化合物,经理化和光谱分析、分别鉴定为白桦脂酸(betulinicacid,1),白桦脂醇(betulin,2),番木鳖甙(loganin,3),睡菜根甙乙(foliamenthin,4),蔗糖(sucrose,5),番木鳖甙元(loganetin,6)。化合物7和8尚在鉴定中,其中化合物5和6为首次从该植物中分得。除对以上8个化合物进行了体外前列腺素生物合成抑制作用的筛选外,并对该植物中的另外2个化合物即羽扇豆醇型三萜α-羽扇豆醇(9)和β-羽扇豆醇(10)亦进行了筛选。结果表明只有羽扇豆醇型三萜1,2,9和10具抑制作用,其中1最有效,其半数抑制浓度IC50为101μM,对照品阿斯匹林的IC₅₀为1879μM,其余3个三萜的IC₅₀分别为白桦脂醇(2)119μM,α-羽扇豆醇(9)为130μM,β-羽扇豆醇(10)为134μM。同时还对羽扇豆醇型三萜类对体外前列腺素生物合成抑制作用作了构效关系的探讨。     

雷公藤红素药理活性与结构修饰研究进展

雷公藤红素是一种天然的木栓烷型五环三萜,卫矛科植物雷公藤（Tripterygium wilfordil Hook.f.）的有效活性成分之一,具有多种药理活性,是目前广受关注的热点天然产物。天然产物及其衍生物是新药开发的重要来源,国内外研究者以雷公藤红素为母核进行大量化学结构修饰研究,并结合活性筛选,发现许多活性更为突出的候选化合物。本文通过对其药理活性和结构修饰的研究进展进行归纳总结,对进一步深入开展药理学研究,以及指导合成新的高效低毒的雷公藤红素衍生物具有重要意义。     

水溶性五环三萜酸衍生物的制备及研究进展

综述几种常见水溶性五环三萜酸衍生物的研究进展。五环三萜酸类化合物多具有广泛的生物活性,但因水溶性差、生物利用度低使其临床应用受到限制。以五环三萜酸为先导化合物,经结构修饰合成水溶性衍生物,并从中寻找出有生物活性和临床应用价值的化合物是当前天然药物化学研究的热点之一。     

桦木属植物三萜类化合物研究进展

植物次生代谢产物是天然药物的重要来源。桦木属植物具有丰富的药用价值,药理作用机制复杂,这与其中的三萜类化合物具有密不可分的关系。桦木属植物三萜类化合物主要分为达玛烷型、奥克梯隆型、齐墩果烷型、羽扇豆烷型和环阿屯烷型;桦木属植物提取物具有抗肿瘤、抗炎、抗氧化、抗菌等多种活性;桦木属植物三萜类化合物的生物合成途径自2,3-氧化鲨烯之后根据环氧角鲨烯环化酶的不同分为达玛烯二醇Ⅱ、羽扇豆醇、环阿屯醇和香树酯四个分支。本文对桦木属植物三萜类化学成分、药理活性和生物合成途径解析三个方面进行了综述,以期为利用桦木属植物三萜类化合物进行新药研发及利用合成生物学方法在微生物细胞工厂中生产这类化合物提供参考。     

冬凌草甲素抗肿瘤作用机制及其结构改造研究进展

天然产物在新药研发中占重要地位,在抗肿瘤药物研究领域,很多活性优良、作用机制和靶点独特的药物都是从活性天然产物中发现的。冬凌草甲素属于ent-贝壳杉烷型二萜化合物,对多种肿瘤具有很好的生长抑制活性。冬凌草甲素的抗肿瘤活性中心为其α,β-不饱和环戊酮结构,其抗肿瘤作用机制涉及细胞凋亡、细胞自噬、细胞周期阻滞等多个方面;近年来,国内外药学工作者针对冬凌草甲素展开了作用机制的深入探索,以及对其提高抗肿瘤活性的结构改造等广泛研究。本文将重点针对这两方面进行综述,期望给药学工作者提供参考。     

山楂酸药理作用的研究进展

山楂酸是一种五环三萜类化合物,广泛存在于油橄榄和山楂等多种天然植物中。山楂酸具有抗肿瘤、抗炎、抗氧化、抗菌、心血管保护、神经保护等药理作用。针对山楂酸的药理活性研究进展及其作用机制进行综述,为其进一步开发和应用提供参考依据。     

Advances in the study of structural modifications and biological activities of betulinic acids

Betulinic acids are lupine-type pentacyclic triterpenoid saponins commonly found in some plants of Betulaceae family, especially in the bark of betula alba (birch). The potent anti-HIV and anti-tumor activities of betulinic acids have been greatly concerned. The natural betulinic acids include betulinic acid, 23-hydroxy betulinic acid, betulin and so on. Some investigations on the structural modifications of betulinic acids were carried out, and many derivatives with excellent biological activity have been obtained nowadays. In this paper, the research advances of the structural modification of betulinic acids, as well as their anti-HIV and anti-tumor activities are reviewed.     

Enhancement of anti-bacterial and anti-tumor activities of pentacyclic triterpenes by introducing exocyclic α,β-unsaturated ketone moiety in ring A

Ursolic acid, oleanolic acid, glycyrrhetinic acid, and betulinic acid, the representatives of pentacyclic triterpenes, were modified by introducing 2-methylene-3-oxo group as exocyclic α,β-unsaturated ketone moiety in ring A. The anti-bacterial and anti-tumor activities of these derivatives were assayed by comparing with the parent compounds. Results indicated that pentacyclic triterpenes carrying 2-methylene-3-oxo group in the ring A exhibited a significant improvement in anti-bacterial activity that was limited to Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis. The four derivatives also showed an increased cytotoxicity against leukemia, lung, and breast cancer cell lines in a dose-dependent manner in vitro. U2 and O2 compounds showed strong apoptotic activities to lung carcinoma cell lines. The results for the first time provided scientific evidence for improvement of anti-bacterial and anti-tumor activities of pentacyclic triterpenes using derivatives of these compounds.     

Betulinic acid exerts immunoregulation and anti-tumor effect on cervical carcinoma (U14) tumor-bearing mice

Phytochemicals used in cancer therapy and prevention are an important source. Betulinic acid (BetA), a lupine-type pentacyclic triterpenoid saponin from plants, has shown anti-tumor activity in some cell lines in previous studies. In this paper, its anti-tumor effect and the possible mechanisms were investigated in U14 tumor-bearing mice. The results showed that BetA (100 mg/kg and 200 mg/kg) effectively suppressed tumor growth in vivo. Compared with the control group, BetA significantly improved the levels of IL-2 and TNF-alpha in tumor-bearing mice and increased the number of CD4+ lymphocytes subsets, as well as the ratio of CD4+/CD8+ at a dose of 200 mg/kg. Furthermore, treatment with BetA induced cells apoptosis in dose-dependent manner in tumor bearing mice, and inhibited the expression of Bcl-2 and Ki-67 protein while upregulated the expression of caspase-8 protein. The mechanisms by which BetA exerted anti-tumor effects might involve the induction of tumor cell apoptosis. This process is also related to improvement of body's immune response.     

熊果酸的研究进展*

熊果酸是存在于植物中的一种三萜类化合物，具有抗肿瘤、抗菌、降血脂等药理作用，现综合国内外文献报道，对熊果酸提取分离方法和含量测定及药理作用等方面进行综述。熊果酸具有广阔的应用前景，亟待开发。     

Betulin binds to gamma-aminobutyric acid receptors and exerts anticonvulsant action in mice

The lupane type pentacyclic triterpenes: lupeol, betulin, and betulinic acid are widely distributed natural compounds. Recently, pharmaceutical compositions from plant extracts (family Marcgraviaceae) containing betulinic acid, have been patented as anxiolytic remedies. To extend our knowledge of the CNS effects of the triterpenes, we suggest here that the chemically related lupeol, betulin and betulinic acid may interact with the brain neurotransmitter γ-aminobutyric acid (GABA) receptors in vitro and in vivo. Using radioligand receptor-binding assay, we showed that only betulin bound to the GABA_A-receptor sites in mice brain in vitro and antagonised the GABA_A-receptor antagonist bicuculline-induced seizures in mice after intracisternal and intraperitoneal administration. Neither betulinic acid nor lupeol bound to GABA_A receptor nor did they inhibit bicuculline-induced seizures in vivo. These findings demonstrate for the first time the CNS effects of betulin in vivo, and they also show distinct GABA_A-receptor-related properties of lupane type triterpenes.These findings may open new avenues in understanding the central effects of betulin, and they also indicate possibilities for novel drug design on the basis of betulin structure.     

Acetyl-boswellic acids are novel catalytic inhibitors of human topoisomerases I and IIalpha

Acetyl-boswellic acids (acetyl-BA) are pentacyclic triterpenes derived from the gum resin of frankincense. We have previously shown that these compounds are effective cytotoxic agents, acting through a mechanism that appears to involve the inhibition of topoisomerase activity. We have now investigated the mechanism of action of acetyl-BA and show that these compounds are more potent inhibitors of human topoisomerases I and IIalpha than camptothecin, and amsacrine or etoposide, respectively. Our data demonstrate that acetyl-BA and, to a lesser extent, some other pentacyclic triterpenes, such as betulinic acid, ursolic acid, and oleanolic acid, inhibit topoisomerases I and IIalpha through a mechanism that does not involve stabilization of the cleavable complex or the intercalation of DNA. Surface plasmon resonance analysis revealed that topoisomerases I and IIalpha bind directly to an immobilized derivative of acetyl-BA. This acetyl-BA derivative interacts with human topoisomerases through high-affinity binding sites yielding K(D) values of 70.6 nM for topoisomerase I and 7.6 nM for topoisomerase IIalpha. Based on our data, we propose that acetyl-BA inhibit topoisomerases I and IIalpha through competition with DNA for binding to the enzyme. Thus, acetyl-BA are a unique class of dual catalytic inhibitors of human topoisomerases I and IIalpha.     

Factors affecting the content of pentacyclic triterpenes in Centella asiatica raw materials

Context: Pentacyclic triterpenes, mainly, asiatic acid, madecassic acid, asiaticoside, and madecassoside are the active constituents of Centella asitica (L.) Urban. (Apiaceae). These compounds possess various pharmacological activities that have been shown to assist with wound healing and brain enrichment.

Objective: Determination of these active pentacyclic triterpenes in extracts from the various parts of C. asiatica plants harvested at different times of the year and grown in different environments.

Materials and methods: The separate plant parts selected were leaves, stolons, petioles, flowers, fruits, and nodes with roots. Dried powder from each part was extracted with ethanol by microwave-assisted extraction and subjected to determination of their content of the four pentacyclic triterpenes using a HPLC method. The effects of the places of cultivation as well as harvesting periods on the content of the four pentacyclic triterpenes in the extracts were also determined.

Results and discussion: Among the various parts of C. asiatica, the leaves contained the highest amount of pentacyclic triterpenes with a total content of pentacyclic triterpenes of 19.5 mg/g dry powder. However, the contents of the pentacyclic triterpenes in C. asiatica varied according to the place of cultivation and the harvesting period. C. asiatica collected from Trang, Thailand gave the highest content of total pentacyclic triterpenes (37.2 mg/g dry powder) when harvested in March, while those collected from Songkhla, Thailand gave the highest value (37.4 mg/g dry powder) when collected in December. C. asiatica collected from Nakornsrithammarat and Ratchaburi, Thailand gave the lowest content of total pentacyclic triterpenes in all experimental harvesting periods.     

熊果酸衍生物构效关系研究进展

综述了近年来对熊果酸的结构修饰及其衍生物构效关系的研究进展。熊果酸是一种广泛存在于天然植物中的五环三萜类化合物,具有抗肿瘤、降血糖、抗炎、抗HIV等药理活性,故而受到研究人员的广泛关注。对熊果酸进行结构修饰及构效关系探索,以获得高效低毒的候选化合物,已成为该化合物的研究热点之一。