Microbial transformation of asiatic acid by Alternaria longipes

Asiatic acid is a major pentacyclic triterpene isolated from Centella asiatica. It shows a variety of bioactivities. In order to obtain its derivatives, potentially useful for detailed pharmacological studies, the substrate was subjected to incubations with selected micro-organisms. In this work, asiatic acid was converted into three new compounds: 2α,3β,23,30-tetrahydroxyurs-12-ene-28-oic acid (1), 2α,3β,22β,23-tetrahydroxyurs-12-ene-28-oic acid (2), and 2α,3β,22β,23,30-pentahydroxyurs-12-ene-28-oic acid (3) by the fungus Alternaria longipes AS 3.2875. The structures of the three metabolites were determined by 1D and 2D NMR spectral data.     

Gastroprotective effect of lupeol on ethanol-induced gastric damage and the underlying mechanism

The effect of lupeol, a natural pentacyclic triterpene on ethanol-induced gastric damage in mice was evaluated. The gastroprotection was assessed by determination of changes in mean gastric lesion area, quantification of mucosal non-protein sulfhydryls (NP-SH), and characterized using drugs that influence the endogenous prostaglandins, α₂-adrenoceptors, nitric oxide, K_ATP-channels, and intracellular calcium. Orally administered lupeol (3, 10, and 30 mg/kg) significantly and dose-dependently attenuated the ethanol-induced gastric damage by 39–69%, whereas the positive control N-acetylcysteine (NAC, 300 mg/kg, i.p.) afforded 32% protection. Both lupeol and NAC restored the NP-SH depleted by ethanol but the lupeol effect was only marginal. Lupeol gastroprotection was attenuated by indomethacin and L-NAME, the respective COX and NO-synthase inhibitors and was weakly sensitive to α₂-adrenergic antagonist yohimbine and K_ATP-channel blocker glibenclamide, but more profoundly to calcium blocker verapamil. These pharmacological effects of lupeol may synergistically contribute to alleviating the ethanol-associated gastric damage, which is multifactorial.     

Synthesis and evaluation of A-seco type triterpenoids for anti-HIV-1protease activity

2,3-Seco-dioic acids derived from four different triterpene skeletons were prepared and evaluated for their anti-HIV-1 protease activity. Two A-seco derivatives showed potent inhibitory activity against HIV-1 protease (3c and 3e, IC₅₀ 5.7 and 3.9 μM, respectively), while four other derivatives showed moderate to weak inhibition (3a, 3b, 3d and 3f, IC₅₀ 15.7–88.1 μM). The combination of a 2,3-seco-2,3-dioic acid functional group in ring A and a free acid group at C-28 or C-30 significantly enhanced HIV-1 protease inhibitory activity (3a, 3c–3e, IC₅₀ 3.9–17.6 μM). On the other hand, all A-seco derivatives were found to be very weak inhibitors of HCV, renin and trypsin proteases (IC₅₀ > 80 μM). These findings indicate that A-seco triterpenes with a carboxyl group at C-28 or C-30 are novel and highly selective HIV-1 protease inhibitors.     

桦褐孔菌三萜的酰化对其抗肿瘤活性的影响

[目的]考察桦褐孔菌中三萜化合物发生酰化成酯后对其抗肿瘤活性的影响。[方法]采用溶剂提取法及硅胶柱层析、ODS开放柱层析和制备型高效液相色谱(HPLC)等从桦褐孔菌子实体中分离制备其代表性羊毛脂烷型三萜,并以此为原料,采用琥珀酸酐进行酰化反应,进而采用噻唑蓝(MTT)法测试原料化合物及其酰化产物对A549、Hela、MCF-7及4T1肿瘤细胞的抑制活性。[结果]从桦褐孔菌中分离并鉴定了化合物inotodiol(1)、trametenolic acid(2)及inonotusane A(3),将他们进行酰化后分别得到inotodiol-3-琥珀酸单酯(1a)、inotodiol-22-琥珀酸单酯(1b)、inotodiol-3,22-琥珀酸二酯(1c)、trametenolic acid-3-琥珀酸单酯(2a)和inonotusane A-3-琥珀酸单酯(3a)。MTT结果表明,化合物1的3-位、22-位酰化后(1a, 1b, 1c)对A549和4T1肿瘤细胞的抑制活性均增强,此外,而其3-位酰化后(1a)还大大增强了对MCF-7肿瘤细胞的抑制活性。化合物2酰化后对活性无影响。化合物3的3-位酰化后对A549、MCF-7及4T1细胞的抑制活性均明显增强,其中对A549表现出最强的抗肿瘤活性(IC50=9.53μmol/L)。[结论]化合物inotodiol(1)的3-位、22-位和inonotusane A(3)的3-位酰化后均增强了其肿瘤活性,为其进一步的结构修饰提供了有价值的参考。     

Selective antileishmania activity of 13,28‐epoxy‐oleanane and related triterpene saponins from the plant families Myrsinaceae,Primulaceae, Aceraceae and Icacinaceae

Maesa saponins with the 13,28‐epoxy‐oleanane triterpene core skeleton were described recently to possess strong and selective in vitro and in vivo antileishmania activity. In the absence of direct chemical derivatization possibilities, a structure‐based literature search was carried out to explore a structure‐activity relationship. Crude alcohol extracts from several plant species of Myrsinaceae, Primulaceae, Aceraceae and Icacinaceae were evaluated for in vitro activity against Leishmania infantum intracellular amastigotes and cytotoxicity on MRC‐5_SV2 cells, while the saponin content was evaluated qualitatively by TLC. A clear correlation was found between the presence of close analogue 13,28‐epoxy‐oleanane triterpene saponins and potent and selective antileishmania activity. This was most striking in Maesa species, except for M. macrosepala. Interesting activities were also found in extracts that did not exactly match the TLC characteristics of the Maesa saponin references, as was the case for Ardisia angusta, A. amherstiana, A. caudata, A. gigantifolia, A. roseiflora, Myrsine affinis, Acer brevipes and A. laurinum var. petelotii. This study indicates that the 13,28‐epoxy‐oleanane triterpene moiety is essential for selective antileishmania potential and that several other plant species could still be explored for antileishmania drug discovery. Copyright © 2009 John Wiley & Sons, Ltd.     

丰城鸡血藤化学成分的研究

目的:分离和鉴定丰城鸡血藤的活性成分.方法:用溶剂法和色谱方法分离化合物,用波谱方法鉴定其结构.结果:从丰城崖豆藤中分离得到10个化合物,其中8个为黄酮类化合物(1～8):毛蕊异黄酮(1),染料木苷(2),gliricidin(3),8-甲雷杜辛(4),阿夫罗摩辛-7-O-β-D-吡喃葡萄糖苷(5),澳白檀苷(6),异甘草素(7)和3,5,7,4'-四羟基-3'-甲氧基黄烷-7-O-β-D-吡喃葡萄糖苷(8);2个为三萜类化合物,羽扇豆醇(9)和无羁萜-3β-醇(10).结论:10个化合物均为首次从该植物中获得.探讨毛蕊异黄酮等在NMR测定中的溶剂效应,纠正了文献[1-2]中该化合物碳谱数据的一些归属错误.     

A New Triterpene Saponin from Gynostemma pentaphyllum

Objective To study the triterpene saponins from Gynostemma pentaphyllum with antitumor activities. Methods The 75% EtOH extract of G. pentaphyllum was used for isolation by silica gel column chromatography and preparative HPLC. The structures of pure compounds isolated were identified by the spectral analysis and chemical evidence. Results Two compounds were isolated and identified as 23(S)-3β,20ξ,21ξ-trihydroxy-19-oxo-21,23-epoxydammar-24-ene 3-O-α-L-rhamnopyranosyl (1→2)-[β-D-xylopyranosyl (1→3)]-β-D-arab...     

可疑翼手参皂苷ColochirosideA体外抑制多种瘤细胞株增殖的研究

目的：研究可疑翼手参体内三萜皂苷ColochirosideA（cA）的体外抗肿瘤活性。方法：用稻瘟霉分生孢子模型对CA进行生物活性初筛,分别用MTT、SRB法检测CA对5种体外培养肿瘤细胞（BEL-7402、HO-8910、MDA—MB-435、MDA—MB-468、A431）和2种体外培养人血管内皮细胞（HMEC、HUVEC）的增殖抑制活性。结果：cA对稻瘟霉显示较强的抑制活性,最小活性浓度（MMDC）〈7．9ug／ml;对5种体外培养人肿瘤细胞显示显著抑制增殖活性,IC50为1．75ug／ml-3．66ug／ml;对2种体外培养人血管内皮细胞均显示显著抑制增殖活性,IC50值分别为2．55ug／ml和5．63ug／ml。结论：CA体外对多种肿瘤细胞具有抑制活性,有进一步研究开发的前景。     

五柱五桠果的化学成分及其体外抗肿瘤抗缺氧活性

目的 研究五柱五桠果的化学成分及其抗肿瘤抗缺氧活性。方法 利用各种色谱技术分离化学成分,根据理化性质与光谱数据鉴定结构,利用MTT法测试抗肿瘤活性。结果 从五柱五桠果果实中分离鉴定了白桦酸 (1)、白桦醇 (2)、羽扇豆醇 (3)、谷甾醇 (4)、没食子酸 (5)、没食子酸乙酯 (6)、原儿茶酸 (7)、原儿茶酸甲酯 (8)。化合物1~3、5和6对K562细胞增殖有抑制活性,其中1、2、5的作用较强,IC50分别为31 μg&;#8226;mL-1、29 μg&;#8226;mL-1、23 μg&;#8226;mL-1;3和6次之,在100 μg&;#8226;mL-1浓度下增殖抑制率分别为26.1 %和31.3 %。化合物5和6在无细胞毒的浓度下对 ECV304 细胞的缺氧损伤有保护作用。结论 化合物1~8系首次从该植物分离得到,其中1~3、5和6为该植物生物活性成分的首例报道。     

Mechanism of action and inhibition of dehydrosqualene synthase

"Head-to-head" terpene synthases catalyze the first committed steps in sterol and carotenoid biosynthesis: the condensation of two isoprenoid diphosphates to form cyclopropylcarbinyl diphosphates, followed by ring opening. Here, we report the structures of Staphylococcus aureus dehydrosqualene synthase (CrtM) complexed with its reaction intermediate, presqualene diphosphate (PSPP), the dehydrosqualene (DHS) product, as well as a series of inhibitors. The results indicate that, on initial diphosphate loss, the primary carbocation so formed bends down into the interior of the protein to react with C2,3 double bond in the prenyl acceptor to form PSPP, with the lower two-thirds of both PSPP chains occupying essentially the same positions as found in the two farnesyl chains in the substrates. The second-half reaction is then initiated by the PSPP diphosphate returning back to the Mg(2+) cluster for ionization, with the resultant DHS so formed being trapped in a surface pocket. This mechanism is supported by the observation that cationic inhibitors (of interest as antiinfectives) bind with their positive charge located in the same region as the cyclopropyl carbinyl group; that S-thiolo-diphosphates only inhibit when in the allylic site; activity results on 11 mutants show that both DXXXD conserved domains are essential for PSPP ionization; and the observation that head-to-tail isoprenoid synthases as well as terpene cyclases have ionization and alkene-donor sites which spatially overlap those found in CrtM.