Cytotoxic Mannopyranosides of Indole Alkaloids from Zanthoxylum nitidum

Three new mannopyranosides of indole alkaloids, methyl 7‐(β‐D ‐mannopyranosyloxy)‐1H‐indole‐2‐carboxylate ( 1 ), methyl 7‐[(3‐O‐acetyl‐β‐D ‐mannopyranosyl)oxy]‐1H‐indole‐2‐carboxylate ( 2 ), and 2‐methyl‐1H‐indol‐7‐yl β‐D ‐mannopyranoside ( 3 ), were isolated from an EtOH extract of the roots of Zanthoxylum nitidum. Their structures were identified as new compounds on the basis of the spectroscopic analyses. Bioactivity evaluation revealed that these alkaloids possess significant cytotoxicities against all the tested tumor cell lines with IC₅₀ values of less than 30 μM .     

Indole alkaloids from cell suspension cultures of Rauwolfia serpentina benth

Twelve indole alkaloids belonging to the Ajmaline-, Sarpagine-, Yohimbine-, and Heteroyohimbine-type have been isolated and identified from cell suspension cultures of Rauwolfia serpentina. Ten of the alkaloids were found for the first time in cultured R. serpentina cells. The yield of the main alkaloid vomilenine was 51 times more than that of differentiated plants. Crude enzymes isolated from this cell suspension culture completely metabolize the biogenetic precursor strictosidine under formation of several alkaloidal compounds.     

Indole Alkaloids from the Sea Anemone Heteractis aurora and Homarine from Octopus cyanea

The two new indole alkaloids 2‐amino‐1,5‐dihydro‐5‐(1H‐indol‐3‐ylmethyl)‐4H‐imidazol‐4‐one ( 1 ), 2‐amino‐5‐[(6‐bromo‐1H‐indol‐3‐yl)methyl]‐3,5‐dihydro‐3‐methyl‐4H‐imidazol‐4‐one ( 2 ), and auramine ( 3 ) have been isolated from the sea anemone Heteractis aurora. Both indole alkaloids were synthesized for the confirmation of the structures. Homarine ( 4 ), along with uracil ( 5 ), hypoxanthine ( 6 ), and inosine ( 7 ) have been obtained from Octopus cyanea.     

Three New Isomeric Indole Alkaloids from Nauclea officinalis

Three new isomeric monoterpene indole alkaloids, naucleofficines I–III ( 1 – 3 , resp.) were isolated from the stems (with bark) of Nauclea officinalis. Their structures were elucidated on the basis of spectroscopic methods and single‐crystal diffraction analyses. The cytotoxic activities of 1 – 3 against human colon cancer, human gastric cancer, and human hepatoma cells were also investigated.     

Three New Indole Diketopiperazine Alkaloids from Aspergillus ochraceus

Asperochramides A – D ( 1  –  4 ), a new natural product and three new indole diketopiperazine alkaloids, along with seven known analogs ( 5  –  11 ), were isolated from the ethyl acetate extract of Aspergillus ochraceus. Their structures were elucidated by extensive spectroscopic analyses, ECD calculation, and single‐crystal X‐ray diffraction analysis. Compounds 3 and 4 represent a rare group of indole diketopiperazine alkaloid with a 3‐hydroxyl‐2‐indolone moiety. The in vitro anti‐inflammatory effects of compounds 1 and 3  –  11 were investigated by using LPS‐stimulated murine macrophage RAW 264.7 cells. Compounds 1 , 8 , 10 , and 11 showed potential anti‐inflammatory activities.     

A Compound Containing Substituted Indole Ligand from a Hyperaccumulator Sedum Alfredii Hance Under Zn Exposure

Sedum alfredii Hance is a fast-growing and high-biomass zinc (Zn) hyperaccumulator native to China. A compound containing substituted indole ligand was isolated from this Zn hyperaccumulator plants by sonication/ethanol extraction, macroporous resin column as well as preparative HPLC (P-HPLC). Hydroponic experiment showed that the concentrations of both Zn and the compound containing substituted indole ligand were remarkably increased in stems and leaves of both hyperaccumulator and non-hyperaccumulator as Zn rising from 0.5 to 50 μmol L^?1, with much more in the stems of hyperaccumulator than non-hyperaccumulator. At 50 μmol L^?1 Zn, hyperaccumulator grew normally but its non-hyperaccumulator suffered from strongly Zn-induced toxicity. This suggested that there was a positive correlation between the compound containing substituted indole ligand and Zn concentration in shoots of hyperaccumulator S. alfredii.     

Indole–porphyrin hybrids produced by metagenomics

New indole–porphyrin hybrid molecules were isolated from Escherichia coli harboring metagenomic DNA from the Japanese marine sponge Discodermia calyx. The indole was appended to the reactive vinyl substituent of the harderoporphyrin chromophore, encoded by the insert DNA. Thus, the chimeric pathway between the heterologously expressed porphyrins and the endogenous indole generated new indole-conjugated chiral porphyrins in E. coli.     

Indole alkaloids from Alstonia scholaris

A new indole alkaloid, alstonamine and a sitsirikine type indole alkaloid, rhazimanine, have been isolated from the leaves of Alstonia scholaris.     

Penicamedine A,a Highly Oxygenated Hexacyclic Indole Alkaloid from Penicillium camemberti

A highly oxygenated hexacyclic indole alkaloid, penicamedine A ( 1 ), bearing a rare furan ring, was isolated from the culture broth of Penicillium camemberti, together with two known analogs, iso‐α‐cyclopiazonic acid ( 2 ) and cyclopiazonic acid ( 3 ). The structure of 1 was elucidated by comprehensive spectroscopic analyses including NMR and HR‐ESI‐MS. Its absolute configuration was further confirmed unambiguously by single‐crystal X‐ray diffraction analysis. Compound 1 was evaluated for anti‐HIV activity with p24 assays and tested for cytotoxic activities against five human cancer cell lines, including HL‐60, SMMC‐7721, A‐549, MCF‐7, SW480, and the immortalized non‐cancerous human pulmonary epithelial cell line BEAS‐2B by MTS method.     

Synthesis of l-Tryptophan from Pyruvate,Ammonia and Indole

The tryptophanase activity which synthesizes l-tryptophan from pyruvate, ammonia and indole, was found to be widely distributed in cells of bacteria belonging to Enterobacteriaceae, such genera as Escherichia, Kluyvera, Enterobacter, Erwinia and Proteus. With the cells of Proteus rettgeri, equilibrium of the elimination reaction of l-tryptophan in the presence of high concentration of ammonia was studied. It was found that the equilibrium inclines toward the synthetic state.

When 5-hydroxy- and 5-methyl-indole were substituted for indole, 5-hydroxy- and 5-methyl-l-tryptophan, respectively, were synthesized. The synthesis of l-tryptophan was also observed with indole and various amino acids, S-methyl-l-cysteine, S-ethyl-l-cysteine, l-cysteine, 5-fluoro-dl-tryptophan, or oxalacetic acid.     

Tenualexin,Other Phytoalexins and Indole Glucosinolates from Wild Cruciferous Species

In general, the chemodiversity of phytoalexins, elicited metabolites involved in plant defense mechanisms against microbial pathogens, correlates with the biodiversity of their sources. In this work, the phytoalexins produced by four wild cruciferous species (Brassica tournefortii, Crambe abyssinica (crambe), Diplotaxis tenuifolia (sand rocket), and Diplotaxis tenuisiliqua (wall rocket)) were identified and quantified by HPLC with photodioarray and electrospray mass detectors. In addition, the production of indole glucosinolates, biosynthetic precursors of cruciferous phytoalexins, was evaluated. Tenualexin, (=2‐(1,4‐dimethoxy‐1H‐indol‐3‐yl)acetonitrile), the first cruciferous phytoalexin containing two MeO substituents in the indole ring, was isolated from D. tenuisiliqua, synthesized, and evaluated for antifungal activity. The phytoalexins cyclobrassinin and spirobrassinin were detected in B. tournefortii and C. abyssinica, whereas rutalexin and 4‐methoxybrassinin were only found in B. tournefortii. D. tenuifolia, and D. tenuisiliqua produced 2‐(1H‐indol‐3‐yl)acetonitriles as phytoalexins. Because tenualexin appears to be one of the broad‐range antifungals occurring in crucifers, it is suggested that D. tenuisiliqua may have disease resistance traits important to be incorporated in commercial breeding programs.     

Competitive Induction and Enhancement of Indole and a Diketopiperazine in Marine Bacteria

Thirteen bacterial strains isolated from a sample of Ulva californica were cultured, extracted, and assayed for antibiotic activity. The target strains were 2 gram-positive isolates from the same algal sample. When cultured in monoculture, 2 of the 13 isolates produced extracts with antimicrobial activity. More significantly, one Bacillus isolate (UA-094) produced indole and cyclo(Phe-Pro) at active levels upon challenge with a different Bacillus target strain. These mildly antibiotic compounds were barely detectable in extracts without challenge. This technique of competitive induction and enhancement could be a valuable tool in the search for new antibiotics.     

Indole Glucosinolates and Camalexin do not Influence the Development of the Clubroot Disease in Arabidopsis thaliana

Root galls of Brassicaceae caused by Plasmodiophora brassicae are dependent on increased auxin and cytokinin formation. In this study we investigated whether indole glucosinolates are involved in indole‐3‐acetic acid (IAA) biosynthesis in root galls, by using a genetic approach. The cytochrome P450 enzymes, CYP79B2 and CYP79B3, convert tryptophan to indole‐3‐acetaldoxime (IAOx), which is a precursor for indole glucosinolates and the phytoalexin camalexin in Arabidopsis thaliana. Root galls of the Arabidopsis ecotypes Wassilewskija (WS) and Columbia (Col) accumulated camalexin, WS at levels up to 320 μg/g dry weight. By contrast, camalexin was absent in root galls of cyp79b2/b3 double mutants. Infection rate and disease index as a measure of club development in mutant and wild‐type plants of the two ecotypes were investigated and no differences were found in gall formation. This demonstrates that camalexin is an ineffective inhibitor of P. brassicae and indole glucosinolates are not the source of elevated levels of IAA in galls, because free IAA levels in mutant galls were comparable with those in wild type.     

Occurrence of Indole Alkaloids among Secondary Metabolites of Soil Aspergillus Spp.

The occurrence of indole alkaloids among secondary fungal metabolites was studied in species of the genus Aspergillus, isolated from soils that were sampled in various regions of Russia (a total of 102 isolates of the species A. niger, A. phoenicis, A. fumigatus, A. flavus, A. versicolor, A. ustus, A. clavatus, and A. ochraceus). Clavine alkaloids were represented by fumigaclavine B, which was formed by A. fumigatus. -Cyclopiazonic acid was formed by isolates of A. fumigatus, A. flavus, A. versicolor, A. phoenicis, and A. clavatus. The occurrence of indole-containing diketopiperazine alkaloids was documented for isolates of A. flavus, A. fumigatus, A. clavatus, and A. ochraceus. No indole-containing metabolites were found among the metabolites of A. ustus or A. niger.     

Indole alkaloids from Hunteria zeylanica

Fourteen indole alkaloids were isolated and identified from the leaves and bark of Hunteria zeylanica: isocorymine, vobasine, (+)-eburnamenine, eburnamine, isoeburnamine, O-ethyleburnamine, O-methyleburnamine, O-methylisoeburnamine, pleiocarpamine, dihydrocorynantheol, yohimbol, epiyohimbol, tuboxenine and hydroxy-17-decarbomethoxy-16-dihydroepiajmalicine. O-Ethyleburnamine, O-methylisoeburnamine, epiyobimbol and hydroxy-17-decarbomethoxy-16-dihydroepiajmalicine, although known products, were isolated for the first time from a natural source.     

Purification and Characterization of a New Indole Oxygenase from the Leaves of Tecoma stans L

A new indole oxygenase from the leaves of Tecoma stans was isolated and purified to homogenity. The purified enzyme system catalyzes the conversion of indole to anthranilic acid. It is optimally active at pH 5.2 and 30°C. Two moles of oxygen are consumed and one mole of anthranilic acid is formed for every mole of indole oxidized. Dialysis resulted in complete loss of the activity. The inactive enzyme could be reactivated by the addition of concentrated dialysate. The enzyme is not inhibited by copper-specific chelators, non-heme iron chelators or atebrin. It is not a cuproflavoprotein, unlike the other indole oxygenases and oxidases.     

Light-Dependent Transformation of Aniline to Indole Esters by the Purple Bacterium Rhodobacter sphaeroides OU5

In an attempt to understand the aromatic hydrocarbon metabolism by purple bacteria that do not grow at their expense, we earlier reported 2-aminobenzoate transformation by a purple non-sulfur bacterium, Rhodobacter sphaeroides OU5 (Sunayana et al., 2005, J Ind Microbiol Biotech 32:41–45), which is extended in the present study with aniline, a major environmental pollutant. Aniline did not support photo (light anaerobic) or chemo (dark aerobic) heterotrophic growth of Rhodobacter sphaeroides OU5 either as a sole source of carbon or nitrogen. However, light-dependent aniline transformation was observed in the culture supernatants and the products were identified as indole derivatives. The transformation was dependent on a tricarboxylate intermediate, fumarate. Five intermediates of the aniline biotransformation pathway were isolated and identified as indole esters having a mass of 443, 441, 279, 189, and 167 with unstoichiometric total indole yields of 0.16 mM from 5 mM of aniline consumed. The pathway proposed based on these intermediates suggest a novel xenobiotic detoxification process in bacteria.     

News & Notes Indole Acetic Acid and Its Metabolism in Root Nodules of a Monocotyledonous Tree Roystonea regia

A monocotyledonous tree, Roystonea regia, was found to bear root nodules. The root nodules contained a high amount (16.9 μg/g fresh mass) of indole acetic acid (IAA). A big tryptophan pool (1555.1 μg/g fresh mass) was found in the root nodules, which might serve as a source of IAA production. The presence of IAA-metabolizing enzymes IAA oxidase and peroxidase indicated metabolism of IAA in the root nodules. The symbiont isolated from the root nodules of R. regia, a Rhizobium sp., produced high amount of IAA in culture when supplemented with tryptophan. The possible role of this IAA production in the monocotyledonous tree–Rhizobium symbiosis is discussed. Received: 31 December 1997 / Accepted: 5 February 1998     

Indole glucosinolate breakdown and its biological effects

Most species in the Brassicaceae produce one or more indole glucosinolates. In addition to the parent indol-3-ylmethylglucosinolate (IMG), other commonly encountered indole glucosinolates are 1-methoxyIMG, 4-hydroxyIMG, and 4-methoxyIMG. Upon tissue disruption, enzymatic hydrolysis of IMG produces an unstable aglucone, which reacts rapidly to form indole-3-acetonitrile and indol-3-ylmethyl isothiocyanate. The isothiocyanate, in turn, can react with water, ascorbate, glutathione, amino acids, and other plant metabolites to produce a variety of physiologically active indole compounds. Myrosinase-initiated breakdown of the substituted indole glucosinolates proceeds in a similar manner to that of IMG. Induction of indole glucosinolate production in response to biotic stress, experiments with mutant plants, and artificial diet assays suggest a significant role for indole glucosinolates in plant defense. However, some crucifer-feeding specialist herbivores recognize indole glucosinolates and their breakdown products as oviposition and/or feeding stimulants. In mammalian diets, IMG can have both beneficial and deleterious effects. Most IMG breakdown products induce the synthesis of phase 1 detoxifying enzymes, which may in some cases prevent carcinogenesis, but in other cases promote carcinogenesis. Recent advances in indole glucosinolate research have been fueled by their occurrence in the well-studied model plant Arabidopsis thaliana. Knowledge gained from genetic and biochemical experiments with A. thaliana can be applied to gain new insight into the ecological and nutritional properties of indole glucosinolates in other plant species.     

Induction of Biofilm Formation in the Betaproteobacterium Burkholderia unamae CK43B Exposed to Exogenous Indole and Gallic Acid

Burkholderia unamae CK43B, a member of the Betaproteobacteria that was isolated from the rhizosphere of a Shorea balangeran sapling in a tropical peat swamp forest, produces neither indole nor extracellular polymeric substances associated with biofilm formation. When cultured in a modified Winogradsky''s medium supplemented with up to 1.7 mM indole, B. unamae CK43B maintains its planktonic state by cell swelling and effectively degrades exogenous indole. However, in medium supplemented with 1.7 mM exogenous indole and 1.0 mM gallic acid, B. unamae CK43B produced extracellular polymeric substances and formed a biofilm. The concentration indicated above of gallic acid alone had no effect on either the growth or the differentiation of B. unamae CK43B cells above a certain concentration threshold, whereas it inhibited indole degradation by B. unamae CK43B to 3-hydroxyindoxyl. In addition, coculture of B. unamae CK43B with indole-producing Escherichia coli in nutrient-rich Luria-Bertani medium supplemented with 1.0 mM gallic acid led to the formation of mixed cell aggregates. The viability and active growth of B. unamae CK43B cells in a coculture system with Escherichia coli were evidenced by fluorescence in situ hybridization. Our data thus suggest that indole facilitates intergenus communication between indole-producing gammaproteobacteria and some indole-degrading bacteria, particularly in gallic acid-rich environments.