Guanidine Alkaloids from Monanchora arbuscula: Chemistry and Antitumor Potential

Five guanidine alkaloids, mirabilin B ( 1 ), 8bβ‐hydroxyptilocaulin ( 2 ), ptilocaulin ( 3 ), and a mixture of the 8β‐ and 8α‐epimers, 4 and 5 , of 8‐hydroxymirabilin (1,8a;8b,3a‐didehydro‐8‐hydroxyptilocaulin), were isolated from Monanchora arbuscula colonies collected off the northeastern Brazilian coast. All structures were elucidated by spectroscopic analysis, including 1D (¹H‐, ¹³C‐ (BB), and ¹³C‐DEPT) and 2D (COSY, HSQC, and HMBC) NMR experiments, and comparison with the literature data. The cytotoxicity of the isolated compounds were evaluated against four tumor cell lines, showing that mirabilin B ( 1 ) and the two epimers were inactive, while 8bβ‐hydroxyptilocaulin ( 2 ) and ptilocaulin ( 3 ) presented IC₅₀ values in the range of 7.9 to 61.5 μM , and 5.8 to 40.0 μM , respectively. Further studies on the mechanism of action of ptilocaulin, using HL‐60 leukemia cells, demonstrated that this guanidine compound induced apoptosis of the treated cells.     

02428×合系35的RIL群体糙米总黄酮与总生物碱含量的遗传分析

测定了水稻02428与合系35杂交培育的222个RIL(重组自交系)及其亲本的发芽糙米和糙米总黄酮和生物碱含量,对其进行遗传分析及探讨了发芽糙米和糙米中总黄酮、生物碱的含量变化.结果表明,RIL群体发芽糙米和糙米中总黄酮、生物碱呈现广泛的遗传变异,糙米总黄酮含量略高于发芽糙米,但两者均呈正态分布,类似于性状的分布特征.RIL群体发芽糙米生物碱含量是糙米的1.5倍,且两者呈偏态分布;为功能水稻的遗传及品种选育提供了一定的理论依据.     

Secondary metabolites produced by mangrove endophytic fungus Aspergillus fumigatus HQD24 with immunosuppressive activity

Immunosuppressive activity guided chemical investigation, four alkaloids (1–4) and eight polyketides (5–12) were isolated from mangrove-derived Aspergillus fumigatus HQD24. Their structures were elucidated unambiguously based on the comprehensive spectroscopic analysis and comparison with literature data. Compounds 1 and 3–5 were separated from mangrove endophytic fungi for the first time, 3 and 12 were firstly recovered from fungal genus Aspergillus. Compound 5 remarkable inhibited proliferation of ConA (concanavalin A)-induced T and LPS (lipopolysaccharide)-induced B murine spleen lymphocytes, with IC₅₀ of 12.11 ± 0.11 μM and 62.66 ± 0.80 μM, respectively. Meanwhile, the chemotaxonomic relations of isolated compounds and Aspergillus species were also discussed.     

Methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase as a target for bis-indole alkaloids with antibacterial activities

Novel classes of antimicrobials are needed to address the emergence of multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). We have recently identified pyruvate kinase (PK) as a potential novel drug target based upon it being an essential hub in the MRSA interactome (Cherkasov, A., Hsing, M., Zoraghi, R., Foster, L. J., See, R. H., Stoynov, N., Jiang, J., Kaur, S., Lian, T., Jackson, L., Gong, H., Swayze, R., Amandoron, E., Hormozdiari, F., Dao, P., Sahinalp, C., Santos-Filho, O., Axerio-Cilies, P., Byler, K., McMaster, W. R., Brunham, R. C., Finlay, B. B., and Reiner, N. E. (2011) J. Proteome Res. 10, 1139-1150; Zoraghi, R., See, R. H., Axerio-Cilies, P., Kumar, N. S., Gong, H., Moreau, A., Hsing, M., Kaur, S., Swayze, R. D., Worrall, L., Amandoron, E., Lian, T., Jackson, L., Jiang, J., Thorson, L., Labriere, C., Foster, L., Brunham, R. C., McMaster, W. R., Finlay, B. B., Strynadka, N. C., Cherkasov, A., Young, R. N., and Reiner, N. E. (2011) Antimicrob. Agents Chemother. 55, 2042-2053). Screening of an extract library of marine invertebrates against MRSA PK resulted in the identification of bis-indole alkaloids of the spongotine (A), topsentin (B, D), and hamacanthin (C) classes isolated from the Topsentia pachastrelloides as novel bacterial PK inhibitors. These compounds potently and selectively inhibited both MRSA PK enzymatic activity and S. aureus growth in vitro. The most active compounds, cis-3,4-dihyrohyrohamacanthin B (C) and bromodeoxytopsentin (D), were identified as highly potent MRSA PK inhibitors (IC(50) values of 16-60 nM) with at least 166-fold selectivity over human PK isoforms. These novel anti-PK natural compounds exhibited significant antibacterial activities against S. aureus, including MRSA (minimal inhibitory concentrations (MIC) of 12.5 and 6.25 μg/ml, respectively) with selectivity indices (CC(50)/MIC) >4. We also report the discrete structural features of the MRSA PK tetramer as determined by x-ray crystallography, which is suitable for selective targeting of the bacterial enzyme. The co-crystal structure of compound C with MRSA PK confirms that the latter is a target for bis-indole alkaloids. It elucidates the essential structural requirements for PK inhibitors in "small" interfaces that provide for tetramer rigidity and efficient catalytic activity. Our results identified a series of natural products as novel MRSA PK inhibitors, providing the basis for further development of potential novel antimicrobials.     

Identification of unprecedented purine-containing compounds, the zingerines, from ginger rhizomes (Zingiber officinale Roscoe) using a phase-trafficking approach

Three unprecedented purine-containing compounds, named [6]-, [8]-, and [10]-zingerines as they are 5-(6-amino-9H-purin-9-yl) analogs of [6]-, [8]-, and [10]-gingerols, respectively, were isolated from a methanolic extract of ginger rhizomes using a phase trafficking-based method that utilizes solid phase reagents allowing for fast and selective simultaneous separation of basic, acidic, and neutral components of natural products extracts.     

Reliance on pollinators predicts defensive chemistry across tobacco species

Defensive traits are typically studied in the context of avoiding antagonists, but may also mediate key interactions with mutualists. Plant chemical defences occur in flowers, suggesting pollinators may be agents of selection on defence. We hypothesised that floral defences would deter pollinators, and therefore, pollinators would select for lower defences in outcrossing than self-pollinating species. We measured pollinator reliance and alkaloid levels in 32 greenhouse-grown Nicotiana species. Using a comparative phylogenetic approach, we found significantly lower nectar, floral and leaf nicotine concentrations in outcrossing than selfing species, with a 15-fold decrease in leaf nicotine levels. Nicotine concentrations were positively correlated across tissues, suggesting that selection against floral defences could constrain the evolution of leaf defences. Thus, pollinators could shape the evolution not only of floral defences but also of defences in other tissues where herbivores have traditionally been considered the dominant agent of selection.     

Cytotoxic Tetraprenylated Alkaloids from the South China Sea Gorgonian Euplexaura robusta

Nine achiral tetraprenylated alkaloids, including three new compounds, named malonganenones I–K ( 1 – 3 , resp.), together with six known analogs, 4 – 9 , were isolated from the gorgonian Euplexaura robusta collected from Weizhou Island of Guangxi Province, China. The structures of compounds 1 – 3 were elucidated by extensive spectral analyses, especially of their 1D‐ and 2D‐NMR data. Compounds 1, 4, 6 , and 7 showed moderate cytotoxicities against K562 and HeLa tumor cell lines with IC₅₀ values ranging from 0.35 to 10.82 μM . Compound 6 also showed moderate inhibitory activity against c‐Met kinase at a concentration of 10 μM .     

Effect of variety and harvesting management on the concentration of tannins and alkaloids in tagasaste (Chamaecytisus palmensis)

The first part of this study evaluated contents of hydrolysable tannins (HT) and condensed tannins (CT) of 65 accessions of tagasaste. In the second part, the effects of harvesting stage and growing season on the contents of HT, CT and alkaloids in different plant parts of the widely grown tagasaste variety ‘MOA’ was studied in a randomized complete block design. Regrowths of tagasaste was harvested in one experiment at 4, 6, 8 and 10 months, separated into growing buds, leaves, barks, branches and stems and in another trial at 6 months regrowth during the main rainy, dry and short rainy seasons. The leaves of different tagasaste accessions contained on average 115 g/kg dry matter (DM) HT in a range of 16–197 and 12.5 abs/g NDF CT in a range of 6.9–35.0 abs/g NDF. The edible fractions (growing buds and leaves) were higher in HT and CT contents compared to the structural parts (stems and barks). The leaf fraction contained higher HT and CT (177.2 g/kg DM and 20.1 abs/g NDF) and the HT tended to decline with progressing harvesting stages. High concentration of alkaloids was found in the non-edible fractions, with the highest content in the bark (235 mg/kg) and the lowest in the leaf (40 mg/kg DM) fractions. These levels increased in the fractions from the 4th to the 8th month of harvesting stage and then declined at the 10th month. About 90% of the alkaloids found in tagasaste were sparteine. Higher concentration of HT was found in tagasaste leaves, harvested during the rainy season compared to the dry season. The concentration of CT was low during the main rainy season, while the highest was during the short rainy and dry seasons. Contents of HT and CT were positively correlated (r = 0.25, P<0.01). However, both the HT and CT contents had negative correlation coefficient of r = −0.43 (P<0.001) and r = −0.73 (P<0.001) with alkaloids, respectively. The results of this study showed that varietal selection, and harvesting management could be used as a means to modulate the level of tannins and alkaloids in tagasaste.     

Two new bromotyrosine derivatives from the marine sponge Pseudoceratina sp

Two new bromotyrosine alkaloids, purealidins T and U (1 and 2, resp.), along with five known bromotyrosines 3-7, were isolated from marine sponge Pseudoceratina sp. Their structures were elucidated on the basis of extensive spectroscopic data (CD, IR, 1D- and 2D-NMR, and MS) analysis.     

A new indole alkaloid and anti-inflammatory constituents from Strychnos cathayensis

A new indole alkaloid, 11,12-dimethoxyhenningsamine, was isolated from the roots of Strychnos cathayensis, together with 19 known compounds. The structure of this new compound was determined through spectroscopic and mass-spectrometric analyses. Among the isolated compounds, 11-methoxyhenningsamine and aesculetin dimethyl ether exhibited potent inhibition (IC(50) < 5.5 microg/ml) on superoxide-anion generation and elastase release by human neutrophils in response to fMet-Leu-Phe/cytochalasin B.