Anticancer and antioxidant tannins from Pimenta dioica leaves

Two galloylglucosides, 6-hydroxy-eugenol 4-O-(6'-O-galloyl)-beta-D-4C1-glucopyranoside (4) and 3-(4-hydroxy-3-methoxyphenyl)-propane-1,2-diol-2-O-(2',6'-di-O-galloyl)-beta-D -4C1-glucopyranoside (7), and two C-glycosidic tannins, vascalaginone (10) and grandininol (14), together with fourteen known metabolites, gallic acid (1), methyl gallate (2), nilocitin (3), 1-O-galloyl-4,6-(S)-hexahydroxydiphenoyl-(alpha/beta)-D-glucopyranose (5), 4,6-(S)-hexahydroxydiphenoyl-(alpha/beta)-D-glucopyranose (6), 3,4,6-valoneoyl-(alpha/beta)-D-glucopyranose (8), pedunculagin (9), casuariin (11), castalagin (12), vascalagin (13), casuarinin (15), grandinin (16), methyl-flavogallonate (17) and ellagic acid (18), were identified from the leaves of Pimenta dioica (Merr.) L. (Myrtaceae) on the basis of their chemical and physicochemical analysis (UV, HRESI-MS, 1D and 2D NMR). It was found that 9 is the most cytotoxic compound against solid tumour cancer cells, the most potent scavenger against the artificial radical DPPH and physiological radicals including ROO*, OH*, and O2-*, and strongly inhibited the NO generation and induced the proliferation of T-lymphocytes and macrophages. On the other hand, 3 was the strongest NO inhibitor and 16 the highest stimulator for the proliferation of T-lymphocytes, while 10 was the most active inducer of macrophage proliferation.     

Cytotoxic bromotyrosine derivatives from a two-sponge association of Jaspis sp. and Poecillastra sp

Bioassay-guided chemical investigation of the lipophilic extract of a two-sponge association (Jaspis sp. and Poecillastra sp.) led to the isolation of two new bromotyrosine derivatives (1 and 2), along with known derivatives (3-12). Cyclobispsammaplin A (1) is a cyclic derivative of the previously reported bispsammaplin A (13), while psammaplin M (2) is composed of beta-alanine (or aspartic acid) unit. Compounds 3, 4, 6, 10, and 12 are isolated for the first time from a sponge belonging to the subclass Tetractinomorpha. Structure elucidation was performed by a combination of high resolution mass and 2D NMR (principally COSY, HMBC, HSQC, and NOESY) spectroscopy. Compounds 1-4, 6, 10, and 12 were evaluated for cytotoxicity against a small panel of five human solid tumor cell lines and their activity was compared in relevance to their structure.     

Effects of some antitumor agents on growth and glycolytic enzymes of the flagellate Crithidia

Some antitumor agents known to specifically inhibit certain tumor cell enzymes were examined for activity against glycolytic enzymes and growth of the insect trypanosomatid, Crithidia fasciculata. The cytoplasmic enzymes hexokinase, alpha-glycerophosphate dehydrogenase, malic dehydrogenase, and glucose-6-phosphate dehydrogenase were tested. Agaricic acid (2-hydroxy-1,2,3-nonadecane tricarboxylic acid) was highly inhibitory (50 to 100%) to malic and alpha-glycerophosphate dehydrogenases at approximately 3 x 10(-5)m; 2-(p-hydroxyphenyl)-2-phenylpropane (2 x 10(-4)m), and 5,6-dichloro-2-benzoxazolinone (5 x 10(-4)m) were less effective (50% inhibition) against them. The antiprotozoal agents primaquine (4 x 10(-4)m) and Melarsoprol (8 x 10(-4)m) were 30 to 40% inhibitory. Agaricic acid, 2-(p-hydroxyphenyl)-2-phenylpropane, and 5,6-dichloro-2-benzoxazolinone inhibited growth of Crithidia at less than 10(-4)m. Eight other test compounds from the Cancer Chemotherapy National Service Center (CCNSC) were not toxic to cell growth, although two (4-biphenylcarboxylic acid and 1-[p-chlorobenzyl]-2-ethyl-5-methyl-indole-3-acetic acid) inhibited Crithidia alpha-glycerophosphate dehydrogenase below 1 mm. All of the compounds used specifically inhibited cancer cell alpha-glycerophosphate dehydrogenase. The corresponding enzyme in pathogenic African trypanosomes is important in their terminal respiration. C. fasciculata may be useful in preliminary evaluation of chemotherapeutic agents as potential trypanocides.     

花生茎叶酚性成分研究

运用大孔树脂对花生茎叶提取液进行富集,不同浓度乙醇洗脱,硅胶、RP-18、Sephadex LH-20等多种材料进一步分离纯化,研究花生茎叶化学成分,并通过理化方法和光谱分析对化合物进行结构鉴定。结果表明:从花生茎叶大孔树脂10%乙醇洗脱部位中分离并鉴定了10个化合物,分别为邻苯二甲酸二异丁酯(1)、水杨酸(2)、儿茶酚(3)、对羟基苯甲酸(4)、(反)-3,4-二羟基苯丙烯酸(5)、对羟基苯酚(6)、邻苯二甲酸二丁酯(7)、3,4-二羟基苯乙醇(8)、对羟基苯乙醇(9)、3,4-二羟基苯甲酸(10)。除化合物1、2和4外,其余均为首次从该植物中分离得到。     

Cytotoxic triterpenoids from the root bark of Helicteres angustifolia

Three new triterpenoids, 3beta-acetoxy-27-[(E)-cinnamoyloxy]lup-20(29)-en-28-oic acid methyl ester (1), 3beta-acetoxy-27-[(4-hydroxybenzoyl)oxy]lup-20(29)-en-28-oic acid (2), and 3beta-acetoxy-27-[(4-hydroxybenzoyl)oxy]olean-12-en-28-oic acid methyl ester (3), together with nine known triterpenoids, 4-12, were isolated from the root bark of Helicteres angustifolia. The structures of these compounds were established on the basis of spectroscopic methods including 2D-NMR experiments. All twelve compounds were tested for their cytotoxic activities against human colorectal cancer (COLO 205), human hepatoma (Hep G2), and human gastric cancer (AGS) cell lines in vitro. Among them, compounds 2, 3, 3beta-O-[(E)-coumaroyl]betulinic acid (6), and pyracrenic acid (7) showed significant cytotoxic activities against human cancer cells COLO 205 and AGS.     

Iridoid glucosides with insecticidal activity from Galium melanantherum

The insecticidal activity of the endemic species Galium melanantherum was evaluated against Crematogaster scutellaris ants and Kalotermes flavicollis termites. Iridoid glucosides 1-7 were isolated for the first time as metabolites of the investigated plant, along with the coumarin scopolin. The main components of the extract were found to be the non-acetylated iridoids: geniposidic acid (1), 10-hydroxyloganin (2), deacetyldaphylloside (3), monotropein (4), deacetylasperulosidic acid (5) and scandoside (6), while asperulosidic acid (7) was present only in minute quantities. All isolated metabolites were identified on the basis of their spectral data. Laboratory bioassays revealed significant levels of toxicity for 1-4 against Kalotermes flavicollis termites and Crematogaster scutellaris ants.     

乳孔硫磺菌的化学成分和抗氧化活性

对乳孔硫磺菌子实体不同极性提取物进行了DPPH和ABTS自由基清除能力的测定,并对氯仿和乙酸乙酯提取物进行了分离纯化。结果表明,乳孔硫磺菌的石油醚、氯仿、乙酸乙酯和甲醇提取物均有一定的抗氧化活性,各提取物对两种自由基的清除能力均表现为甲醇提取物＞乙酸乙酯提取物＞氯仿提取物＞石油醚提取物,甲醇提取物对DPPH自由基的清除率最高可达到93.78%;对ABTS自由基的清除率最高可达到62.06%;从氯仿和乙酸乙酯提取物中分离得到10个化合物,分别是：(22E,24R)-5α,8α-过氧麦角甾-6,22-二烯-3β-醇（1）,阿里红酸 A（2）,麦角甾-7,22-二烯-3β-醇（3）,啤酒甾醇（4）,硫色多孔菌酸（5）,(4E,8E)-N-d-2′-hydroxypalmitoyl-1-O-β-d-glycopyranosyl- 9-methyl-4,8-sphingadienine（6）,麦角甾醇（7）,N-(2′-羟基二十四碳酰基)-1,3,4-三羟基-2-氨基-十八烷（8）,烟酸（9）和齿孔酸（10）。其中,化合物2、6、8和9为首次从硫磺菌属真菌中分离得到。     

New glycosides from Tetracentron sinense and their cytotoxic activity

One novel neolignan (tetracentronsine; 1), one new indole alkaloid (=3-(2-hydroxyethyl)-1H-indole-5-O-beta-D-glucopyranoside; 2), and two new phenol derivatives, 3-{2-[(beta-glucopyranosyl)oxy]-4,5-(methylenedioxy)phenyl}propanoic acid (3) and methyl 3-{2-[(beta-glucopyranosyl)oxy]-4,5-(methylenedioxy)phenyl}propanoate (4), together with six known compounds were isolated from the stem bark of Tetracentron sinense. Their structures were determined by spectral analysis, including 1D- and 2D-NMR, and MS analyses. These compounds were tested for their cytotoxic activity against human leukaemia cells in vitro. Among them, compound 2, (E)-3-(4-hydroxyphenyl)-N-[2-(4-hydroxyphenyl)ethyl]prop-2-enamide (5), and maslinic acid (6) showed significant inhibitory activities against human leukaemia cells CCRF-CEM and its multidrug-resistant sub-line, CEM/ADR5000, with IC50 values in a range of 7.1 to 29.7 microM.     

Redoxcitrinin, a biogenetic precursor of citrinin from marine isolate of fungus Penicillium sp

A chemical analysis of the fermentation of the marine-derived fungus Penicillium sp. led to the isolation of a biogenetic precursor of citrinin, redoxcitrinin (1), together with polyketide mycotoxins, phenol A (2), citrinin H2 (3), 4-hydroxymellein (4), citrinin (5), and phenol A acid (6). The structures of compounds 1-6 were determined on the basis of physicochemical data analyses. Among them, compounds 1-3 exhibited a potent radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) with IC50 values of 27.7, 23.4, and 27.2 microM, respectively.     

Activities of 2,4-dihydroxy-6-n-pentylbenzoic acid derivatives

Esters of 2-hydroxy-4-methoxy-6-n-pentylbenzoic acid (2-8) (methyl, ethyl, butyl, pentyl, isopropyl, sec-butyl and benzyl), olivetol (9), methyl, ethyl, butyl perlatolates (10-12), 2,4-dihydroxy-6-n-pentylbenzoic acid (15), and methyl and ethyl esters of (15) were prepared through structural modifications of perlatolic acid (1) with the aim to detect new antifungal and antibacterial substances and also to evaluate the toxicity by the brine shrimp lethality assay against Artemia salina. The antifungal assays were carried out against the fungus Cladosporium sphaerospermum through the bioautography method, and methyl 2,4-dihydroxy-6-n-pentylbenzoate (13) showed the highest antifungal activity (2.5 yg). Olivetol (9) and 2,4-dihydroxy-6-n-pentylbenzoic acid (15) are also potent inhibitors of the growth of the fungus (5.0 microg). Except for methyl (10), the ethyl (11) and butyl (12) perlatolates were less active than perlatolic acid (1). The activities presented by methyl (2) and ethyl (3) 2-hydroxy-4-methoxy-6-n-pentylbenzoates and methyl (13) and ethyl (14) 2,4-dihydroxy-6-n-pentylbenzo-ates suggest that compounds with a free hydroxy group in the aromatic ring (C-4) have a more pronounced effect against C. sphaerospermum. Antibacterial activities were tested by the disc diffusion method using pathogenic strains of S. aureus and E. coli. The compounds were weakly active with inhibition zones between 9-15 mm. The 2-hydroxy-4-methoxy-6-n-pentylbenzoic esters 2-8 and alkyl perlatolates 10-12 were selective against E. coli. Perlatolic acid (1) and methyl 2-hydroxy-4-methoxy-6-n-pentylbenzoate (2) were the most active with LD50 values of 24.1 microM and 27.2 microM, respectively. The other compounds were not toxic to Artemia salina larvae.     

Triterpenoid saponins with N-acetyl sugar from the bark of Albizia procera

Three (1,2,4) and one known (3) triterpenoid saponins were isolated from the bark of Albizia procera. The saponins were characterized as 3-O-[beta-D-xylopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->6)-2-acetamido-2-deoxy-beta-D-glucopyranosyl] echinocystic acid (1), 3-O-[alpha-L-arabinopyranosyl-(1-->2)-beta-D-fucopyranosyl-(1-->6)-2-acetamido-2-deoxy-beta-D-glucopyranosyl] echinocystic acid (2) and 3-O-[beta-D-xylopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->6)-2-acetamido-2-deoxy-beta-D-glucopyranosyl] acacic acid lactone (4). Their structures were elucidated by 1D and 2D NMR experiments, FABMS as well as chemical means. Saponins 1 and 3 exhibited cytotoxicity against HEPG2 cell line with IC50 9.13 microg/ml and 10 microg/ml, respectively.     

白木香果实化学成分研究

运用柱色谱技术从白木香(Aquilaria sinensis (Lour.) Gilg)果实中分离得到7个化合物,经波谱解析和理化性质分别鉴定为: 3-吲哚甲酸(1)、6-羟基-2-[2-(4-羟基苯基)乙基]色原酮(2)、芫花素(3)、4', 5-二羟基-3',7-二甲氧基黄酮(4)、洋芹素-7,4'-二甲醚(5)、 β-谷甾醇(6)和胡萝卜苷(7)。其中化合物1为首次从瑞香科沉香属植物中分离得到。     

Camphorsulfonic acid catalysed facile tandem double Friedlander annulation protocol for the synthesis of phenoxy linked bisquinoline derivatives and discovery of antitubercular agents

A series of phenoxy linked bisquinoline derivatives were synthesised from the Friedlander annulation of 2-(4-acetylphenoxy)-1-aryl-1-ethanones with 2-aminobenzophenone in good yields using (±)-camphor-10-sulfonic acid (CSA) as the catalyst. These compounds were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB) and among the 23 compounds screened, 2-(3-bromophenyl)-6-chloro-3-[4-(6-chloro-4-phenyl-2-quinolyl)phenoxy]-4-phenylquinoline (3q) and 2-(4-bromophenyl)-6-chloro-3-[4-(6-chloro-4-phenyl-2-quinolyl)phenoxy]-4-phenylquinoline (3o) were found to be the most active compounds with MIC of 1.1 and 2.2 μM against MTB. The cytotoxic effects against mouse fibroblasts (NIH 3T3) in vitro were evaluated for 3o and 3q, which displayed no toxic effects against mouse fibroblast cell line NIH 3T3.     

Evaluation of sage phenolics for their antileishmanial activity and modulatory effects on interleukin-6, interferon and tumour necrosis factor-alpha-release in RAW 264.7 cells

A series of sage phenolics was tested for activity against a panel of Leishmania parasites and for immunomodulatory effects on macrophage functions including release of tumour necrosis factor (TNF), interleukin-6 (IL-6), and interferon (IFN)-like activities. For this, functional bioassays were employed including an in vitro model for leishmaniasis in which macrophage-like RAW 264.7 cells were infected with Leishmania parasites, an extracellular Leishmania growth-inhibition assay, a fibroblast-lysis assay for TNF-activity, a cell proliferation assay using IL-6 sensitive murine B9 hybridoma cells, and a virus protection assay for IFN-like activity. Whereas none of the test samples exhibited marked activities against extracellular Leishmania promastigotes (IC50 > 700 to > 2800 nM; > 500 microg/ml), caffeic acid, salvianolic acids K and L as well as the methyl ester of salvianolic acid I showed pronounced antileishmanial activities against intracellular amastigote stages within RAW cells (IC50 3-23 nM vs. 10-11 nM for the reference Pentostam). Noteworthy, the phenolic samples showed no cytotoxicity against the host cells (IC50 > 600 to > 2200 nM; > 400 microg/ml). Tested sage phenolics activated Leishmania-infected RAW 264.7 for release of TNF ranging 22-117 U/ml and IL-6 ranging 3-42 U/ml. In contrast, their TNF- or IL-6-inducing potential in experiments with non-infected host cells was negligible. Furthermore, caffeic acid and salvianolic acid K induced a modest release of IFN-like activity (5-9 and 2-4 U/ml, respectively) as reflected by inhibition of the cytopathic effect of encephalomyocarditis virus on L929 cells. The results support the emerging picture that plant polyphenols may be credited for the profound health-beneficial properties of various herbal medicines and agricultural products.     

槲寄生中的化学成分及其抗肿瘤活性(Ⅰ)

从槲寄生75%乙醇提取物中分离得到4个化合物,应用波谱学方法鉴定它们的结构为尼克酰胺(1),乙酰胺(2),齐墩果酸(3),β-香树脂醇乙酸酯(4).其中,化合物1和2为首次从槲寄生属植物中分离得到.采用MIT法对化合物1～4进行体外抗肿瘤活性研究,结果显示化合物1、2和4对HO-8910人卵巢浆液性腺癌、SMMC7721人肝癌、T24人膀胱癌、HepG2人肝癌和SHG人神经胶质瘤细胞系没有细胞毒活性,化合物3则对这五种肿瘤细胞系有显著的抑制作用.     

大火草根部的化学成分

大火草（Ａｎｅｍｏｎｅ　ｔｏｍｅｎｔｏｓａａ（Ｍａｘｉｍ．）Ｐｅｉ）根状茎提取物的乙酸乙酯部分对粘虫（ＬｅｕｃａｎｉａｓｅｐａｒａｔａＷａｌｋｅｒ）有较好的非选择性拒食活性。从该部分分离得到１１个化合物,通过ＮＭＲ、ＭＳ等波谱分析确定它们的结构分别为４,５-二甲氧基-７-甲基香豆素（１）、４-甲氧基-５-甲基-６,７-二氧亚甲基香豆素（２）、４,７-二甲氧基-５-甲基香豆素（３）、齐墩果酸（４）、齐墩果酮酸（５）、齐墩果酸-３-Ｏ-β-Ｄ-吡喃木糖甙（６）、β-谷甾醇（７）、豆甾醇（８）、胡萝卜甙（９）、豆甾醇-３-Ｏ-β-Ｄ-吡喃葡萄糖甙（１０）和过氧化麦角甾醇（１１）。这些化学成分均为首次从该植物中分离得到,其中１和２为新化合物。     

An antitumor promoter from Moringa oleifera Lam

In the course of studies on the isolation of bioactive compounds from Philippine plants, the seeds of Moringa oleifera Lam. were examined and from the ethanol extract were isolated the new O-ethyl-4-(alpha-L-rhamnosyloxy)benzyl carbamate (1) together with seven known compounds, 4(alpha-L-rhamnosyloxy)-benzyl isothiocyanate (2), niazimicin (3), niazirin (4), beta-sitosterol (5), glycerol-1-(9-octadecanoate) (6), 3-O-(6'-O-oleoyl-beta-D-glucopyranosyl)-beta-sitosterol (7), and beta-sitosterol-3-O-beta-D-glucopyranoside (8). Four of the isolates (2, 3, 7, and 8), which were obtained in relatively good yields, were tested for their potential antitumor promoting activity using an in vitro assay which tested their inhibitory effects on Epstein-Barr virus-early antigen (EBV-EA) activation in Raji cells induced by the tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA). All the tested compounds showed inhibitory activity against EBV-EA activation, with compounds 2, 3 and 8 having shown very significant activities. Based on the in vitro results, niazimicin (3) was further subjected to in vivo test and found to have potent antitumor promoting activity in the two-stage carcinogenesis in mouse skin using 7,12-dimethylbenz(a)anthracene (DMBA) as initiator and TPA as tumor promoter. From these results, niazimicin (3) is proposed to be a potent chemo-preventive agent in chemical carcinogenesis.     

Antitumor agents. Part 226: synthesis and cytotoxicity of 2-phenyl-4-quinolone acetic acids and their esters

2-Phenyl-4-quinolone acetic acids and their esters were synthesized and evaluated for interaction with tubulin and for cytotoxicity against a panel of human tumor cell lines. 2-Phenyl- and 2-(2'-fluorophenyl)-4-quinolone-8-acetic acids (11 and 12) displayed potent cytotoxicity with ED(50) values at nanomolar concentrations, but had minimal activity against tubulin polymerization. 2-(2'-Fluorophenyl)-4-quinolone-6-acetic acid (3) and 2-(2'-fluorophenyl)-4-quinolone-8-acetic acid methyl ester (10) moderately inhibited tubulin polymerization.     

Acyclic nucleoside/nucleotide analogues with an imidazole ring skeleton

Syntheses of a few acyclic nucleoside and acyclic nucleoside phosphonate analogues containing an imidazole ring have been reported. These analogues include methyl 1-(2-hydroxyethoxymethyl)imidazole-4, 5-dicarbo-xylate (1), 4,5-dicarbamoyl-1-(2-hydroxyethoxymethyl)imidazole (2), 4,5-dicyano-1-(2-hydroxyethoxymethyl)imidazole (4), Methyl 1-(2-bromoethoxymethyl)imidazole-4,5-dicarboxylate (7), 4,5-dicyano-(2-bromoethoxymethyl)imidazole (8), and Methyl 1-(2-phosphonomethoxyethyl)imidazole (10). Also reported are a few potential prodrugs of the above compounds, including the acetyl derivatives 5 and 6 (of 1 and 4, respectively), and the diethyl phosphonate ester 9 (of 10). In addition, the corresponding benzyl-protected precursors 11 and 12 (of 1 and 4, respectively), along with their common hydrolysis product, 1-(2-benzyloxy-ethoxymethyl)-4,5-imidazoledicarboxylic acid (3), are reported. Another potential prodrug included in the list is 1-(2-acetoxyethyl)-4,5-dicyanoimidazole (15). The compounds were screened for in vitro antiviral activity against a wide variety of herpes and respiratory viruses. The most active compound was the phosphonate analogue 9 which exhibited an anti-measles virus activity with an EC50 of <2.5 microg/mL and an SI value of > 176.     

Phytochemicals from the aerial parts of Ligularia thomsonii and their radical scavenging activity

Phytochemical investigation of the aerial parts of Ligularia thomsonii has led to the isolation of three new phenylpropanoid glucosides ligularoside I (1), ligularoside II (2) and ligularoside III (3) along with nine known compounds; cinnamic acid (4), 3-phenylpropanoic acid (5), 3,4,5-trihydroxybenzoic acid (6), 4-hydroxybenzoic acid (7), p-coumaric acid (8), caffeic acid (9), 3,4-dihydroxybenzoic acid (10), kaempferol 3-O-β-d-glucopyranoside (11) and 3,5-di-O-caffeoylquinic acid (12), hitherto unreported from L. thomsonii. Their chemical structures were elucidated by spectroscopic analysis and chemical transformation. All these compounds were tested for antioxidant activity using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. Among them, compounds 9, 10 and 12 showed significant antioxidant activity against DPPH radicals with IC₅₀ of 19.6, 23.3 and 8.9 μm, respectively.