Microbial transformation of 20(S)-protopanaxatriol-type saponins by Absidia coerulea

Three 20(S)-protopanaxatriol-type saponins, ginsenoside-Rg1 (1), notoginsenoside-R1 (2), and ginsenoside-Re (3), were transformed by the fungus Absidia coerulea (AS 3.3389). Compound 1 was converted into five metabolites, ginsenoside-Rh4 (4), 3beta,2beta,25-trihydroxydammar-(E)-20(22)-ene-6-O-beta-D-glucopyranoside (5), 20(S)-ginsenoside-Rh1 (6), 20(R)-ginsenoside-Rh1 (7), and a mixture of 25-hydroxy-20(S)-ginsenoside-Rh1 and its C-20(R) epimer (8). Compound 2 was converted into 10 metabolites, 20(S)-notoginsenoside-R2 (9), 20(R)-notoginsenoside-R2 (10), 3beta,12beta,25-trihydroxydammar-(E)-20(22)-ene-6-O-beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranoside (11), 3beta,12beta-dihydroxydammar-(E)-20(22),24-diene-6-O-beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranoside (12), 3beta,12beta,20,25-tetrahydroxydammaran-6-O-beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranoside (13), and compounds 4-8. Compound 3 was metabolized to 20(S)-ginsenoside-Rg2 (14), 20(R)-ginsenoside-Rg2 (15), 3beta,12beta,25-trihydroxydammar-(E)-20(22)-ene-6-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside (16), 3beta,12beta-dihydroxydammar-(E)-20(22),24-diene-6-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside (17), 3beta,12beta,20,25-tetrahydroxydammaran-6-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside (18), and compounds 4-8. The structures of five new metabolites, 10-13 and 16, were established by spectroscopic methods.     

Microbial O-demethylation, hydroxylation, sulfation, and ribosylation of a xanthone derivative from Halenia elliptica

1-Hydroxy-2,3,5-trimethoxyxanthone (1), one of the major xanthone derivatives isolated from Halenia elliptica, was biotransformed by two fungi, Trichothecium roseum and Paecilomyces marquandii. Transformation of 1 by T. roseumgave 1,5-dihydroxy-2,3-dimethoxyxanthone (2), 5-O-sulfate-1-hydroxy-2,3-dimethoxyxanthone (3), 5-O-sulfate-1-hydroxy-2,3,7-trimethoxyxanthone (4), 5-O-beta-ribofuranosyl-1-hydroxy-2,3-dimethoxyxanthone (5), and 1,5,6-trihydroxy-2,3-dimethoxyxanthone (6). Compound 2 was also formed by P. marquandii. The structures of the isolated compounds were elucidated by spectroscopic analyses. Among the five microbial-converted compounds, 3, 4, 5, and 6 are new compounds.     

Iridoids from the rhizomes and roots of Valeriana jatamansi

Five new iridoids, 1-homoacevaltrate (1), 1-homoisoacevaltrate (2), 11-homohydroxyldihydrovaltrate (3), 10-acetoxy-1-homovaltrate hydrin (4), and 10-acetoxy-1-acevaltrate hydrin (5), along with 10 known analogues, were isolated from the rhizomes and roots of Valeriana jatamansi. Structural elucidation was based on spectroscopic data interpretation.     

Cytotoxic pheophorbide-related compounds from Clerodendrum calamitosum and C. cyrtophyllum

Three pheophorbide-related compounds (1-3) were isolated from the leaves and stems of Clerodendrum calamitosum. The methyl ester of 3 (6) and the known (10S)-hydroxypheophytin a (7) also were isolated from leaves of the related plant Clerodendrum cyrtophyllum. Compounds 1 and 6 were isolated for the first time as naturally occurring products from a plant source. All structures were elucidated by detailed spectroscopic analysis. Biological evaluation showed that 1 and 2 exhibited strong cytotoxicity against human lung carcinoma (A549), ileocecal carcinoma (HCT-8), kidney carcinoma (CAKI-1), breast adenocarcinoma (MCF-7), malignant melanoma (SK-MEL-2), ovarian carcinoma (1A9), and epidermoid carcinoma of the nasopharynx (KB), and its etoposide- (KB-7d), vincristine- (KB-VCR), and camptothecin-resistant (KB-CPT) subclones. Compound 3 was less cytotoxic than 1 and 2. Compounds 4-6, the methyl esters of 1-3, showed strongly increased cytotoxicity compared with the parent acids. Interestingly, 6 was the most active derivative among these compounds. Compound 7 was inactive.     

团状雪灵芝化学成分及其抑制TGF-β1活性

目的研究团状雪灵芝的化学成分及其抑制TGF-β1活性。方法团状雪灵芝90%乙醇提取物采用D101大孔吸附树脂、硅胶、微孔树脂和C₁₈反相制备型高压液相进行分离纯化,根据理化性质及波谱数据鉴定所得化合物的结构。利用脂多糖诱导RAW264.7细胞模型,测定其对TGF-β1的抑制作用。结果从中分离得到16个化合物,分别鉴定为1,2,3,4-四氢-1,3,4-三羰基-β-咔啉(1)、芹菜素-7-O-β-D-葡萄糖苷(2)、β-咔啉-1-羧酸(3)、蚤缀碱A(4)、3,3′,4′-三-O-甲基鞣花酸(5)、木犀草素(6)、咖啡酸(7)、木犀草素-7-O-β-D-葡萄糖苷(8)、芹菜素(9)、柚皮素(10)、槲皮素-3-O-β-D-葡萄糖(11)、鼠李秦素(12)、salcolin A(13)、1-O-feruloylglycerol(14)、4-羟基苯甲醛(15)、dibutyl-phthalate(16)。化合物1、3~4、6、11、13对TGF-β1的IC₅₀值分别为4.95、5.79、7.76、11.55、18.89、15.65μg/mL。结论所有化合物均为首次从该植物中分离得到,化合物1、3~4、6、11、13对TGF-β1有较强的抑制作用。     

Stem bark alkaloids of Rauvolfia caffra

Thirty two alkaloids were isolated from the stem bark of Rauvolfia caffra and 28 were identified. The alkaloids represented corynane (3), strictamine (1), sarpagan (4), akuammicine (2), pleiocarpamine (1), indolenine (1), dihydroindole (6), peraksine (3), heteroyohimbine (2), hydroxyheteroyohimbine (2), oxindole (1), 2-acyl-indole (1), suaveoline (3) and yohimbine (2) types. The anhydronium base serpentine was detected but not isolated. The principal alkaloids were ajmaline and norajmaline (dihydroindoles), ajmalicinine and ajmalicine (heteroyohimbines), geissoschizol (E-seco indole) and pleiocarpamine and the heteroyohimbine derived alkaloids were predominantly normal configuration compounds. The biosynthetic and ethnopharmacological significance of the alkaloids is discussed.     

Isolation and in vitro antiplasmodial activities of alkaloids from Teclea trichocarpa: in vivo antimalarial activity and X-ray crystal structure of normelicopicine

Seven alkaloids have been isolated from Teclea trichocarpa including four, normelicopicine (1), arborinine (2), skimmianine (6), and dictamnine (7), that are reported for the first time in addition to the previously reported alkaloids melicopicine (3), tecleanthine (4), and 6-methoxytecleanthine (5). The structure of 1 was confirmed by single-crystal X-ray crystallography. Two alkaloids, 1 and 2, displayed limited in vitro activities against Plasmodium falciparum strains HB3 and K1, but there appeared to be little cross-resistance with chloroquine. Alkaloid 1 was found to have some activity against P. berghei in mice (32% suppression of parasitaemia at a dose of 25 mg x kg(-1) x day(-1)), but unlike chloroquine it did not inhibit beta-haematin formation in a cell-free system; 1 was found to have low in vitro cytotoxicity to KB cells (IC50 > 328 microM).     

Neurotoxic meroditerpenoids from the tropical marine brown alga Stypopodium flabelliforme

Brine shrimp toxicity and TLC analysis guided the isolation of five new and biologically active meroditerpenoids [2beta,3alpha-epitaondiol (1), flabellinol (2), flabellinone (3), stypotriolaldehyde (4), and stypohydroperoxide (5)] along with five known compounds from the marine brown alga Stypopodium flabelliforme collected in Papua New Guinea. The planar structures of compounds 1-5 were determined by extensive spectroscopic analysis (1D and 2D NMR, LRMS, HRMS, IR, and UV), while relative configuration was determined by 1D and 2D NOE experiments. X-ray crystallography confirmed the relative configuration of 2beta,3alpha-epitaondiol (1), and the modified Mosher's ester method was used to establish its absolute configuration. All of the new metabolites were moderately toxic to murine neuro-2a cells (LC50 2-25 microM), and three [2beta,3alpha-epitaondiol (1), flabellinol (2), and flabellinone (3)] possessed potent sodium channel blocking activity. Stypotriolaldehyde (4) had a biphasic effect on the concentration of intracellular Ca2+ in rat cerebellar granule neurons (CGN). The previously known compound, stypoldione (6), also modulated intracellular calcium concentration and was cytotoxic in CGN. Metabolites 2beta,3alpha-epitaondiol (1), flabellinol (2), and flabellinone (3) displayed moderate cytotoxicity to the NCI-H460 human lung cancer cell line.     

外敷降压膏治疗慢性肾功能不全高血压18例

外敷降压膏主要用药肉桂2份,细辛1份,车前子2份,沉香1份,冰片1份,研末用酒精(95%)调和成膏,外敷于患者双侧肾俞穴,18例慢性肾功能不全高血压患者外敷降压膏后,显效10例(55.6%),有效5例(27.8%),无效3例(16.6%),总有效率83.4%.     

Antineoplastic agents. 400. Synthesis of the Indian Ocean marine sponge cyclic heptapeptide phakellistatin 2

Solution-phase synthesis of the marine sponge constituent phakellistatin 2 (1), cyclo(Tyr-Pro-Phe-Pro-Ile-Ile-Pro), was completed using a combination of stepwise coupling and (4 + 3) segment condensation. Use of diethyl phosphorocyanidate for the peptide bond formations gave the linear heptapeptide in 54% yield. Cyclization was achieved in high yields utilizing TBTU (2), BOP-C1 (3), PyBroP (4), and HOAt (5), resulting in 50-65% yields of phakellistatin 2 (1) depending on the method employed. The synthetic cyclic peptide was chemically but not biologically identical with the natural product.