Seasonal variation in toxic steroidal alkaloids of foothill death camas (Zigadenus paniculatus)

Death camas (Zigadenus spp.) is a common poisonous plant in North America with plants occurring in a wide variety of habitats with species of toxic concern occurring primarily in meadows, grasslands, shrublands, and mountains. The toxicity of Zigadenus species has been attributed to a series of steroidal alkaloids. The objective of this study was to evaluate zygacine and total steroidal alkaloid concentrations in different plant tissues of Zigadenus paniculatus as a function of plant maturity. Death camas plants were collected at two locations at different developmental growth stages representing vegetative, flower, seed pod, and shattered seed pod stages. Zygacine represented greater than 50% of the total steroidal alkaloids at all developmental stages. In bulbs, total steroidal alkaloid and zygacine concentrations did not change significantly as a function of plant phenology, and concentrations were lower than what were observed in above ground plant parts. Total steroidal alkaloid and zygacine concentrations in above ground parts were highest at early vegetative growth stages and decreased over the growing season. In plant reproductive parts, total steroidal alkaloid and zygacine concentrations increased until maturity and then decreased as the plant senesced. The concentrations of steroidal alkaloids reported here suggest that the toxic risk associated with death camas is greatest in the early vegetative growth stages followed by the flower and pod stages. There is a toxic risk to livestock as long as the plant is present, and caution should be taken when grazing livestock in areas with death camas until the plant senesces.     

Modulation of interaction of mutant TP53 and wild type BRCA1 by alkaloids: a computational approach towards targeting protein-protein interaction as a futuristic therapeutic intervention strategy for breast cancer impediment

Protein–protein interactions (PPI) are a new emerging class of novel therapeutic targets. In order to probe these interactions, computational tools provide a convenient and quick method towards the development of therapeutics. Keeping this in view the present study was initiated to analyse interaction of tumour suppressor protein p53 (TP53) and breast cancer associated protein (BRCA1) as promising target against breast cancer. Using computational approaches such as protein–protein docking, hot spot analyses, molecular docking and molecular dynamics simulation (MDS), stepwise analyses of the interactions of the wild type and mutant TP53 with that of wild type BRCA1 and their modulation by alkaloids were done. Protein–protein docking method was used to generate both wild type and mutant complexes of TP53-BRCA1. Subsequently, the complexes were docked using sixteen different alkaloids, fulfilling ADMET and Lipinski’s rule of five criteria, and were compared with that of a well-known inhibitor of PPI, namely nutlin. The alkaloid dicentrine was found to be the best docked alkaloid among all the docked alklaloids as well as that of nutlin. Furthermore, MDS analyses of both wild type and mutant complexes with the best docked alkaloid i.e. dicentrine, revealed higher stability of mutant complex than that of the wild one, in terms of average RMSD, RMSF and binding free energy, corroborating the results of docking. Results suggested more pronounced interaction of BRCA1 with mutant TP53 leading to increased expression of mutated TP53 thus showing a dominant negative gain of function and hampering wild type TP53 function leading to tumour progression.     

正交设计和动态过程优化两面针超声提取工艺

以总生物碱提取率为指标,先用正交试验优化两面针的超声提取工艺,再动态过程精选提取工艺。最佳工艺条件为:复合酶预处理后,以体积分数60%乙醇(盐酸5 g/L)超声(250 W)提取3次,第1次以10倍量溶剂提取15 min,第2次以4倍量溶剂提取12 min,第3次以3倍量溶剂提取9 min,总生物碱提取率87.80%。该工艺高效、节能、省时,为工业生产奠定了实验基础。     

New Antibacterial Diterpenoids from the Sarcodon scabrosus Fungus

The structures of new antibacterial diterpenoids that had been isolated from Sarcodon scabrosus were established by chemical and spectral means to be sarcodonin L (2) and M (3), both having the cyathane skeleton. Other antibacterial compounds were identified to be allocyathin B₂ (1), sarcodonin G (4) and sarcodonin A (5) by comparing their spectral data with those of authentic samples.     

Hybridisation in Jacobaea – characterisation of hybrids between Jacobaea aquatica and J. vulgaris in Austria

Background: Hybridisation in Senecio/Jacobaea is frequent and of significance in speciation and evolution. Moreover, these genera are model systems for studying the evolution of pyrrolizidine alkaloids (PAs). Hybrids between Jacobaea aquatica and J. vulgaris have been reported from north-western Europe.

Aims: Our aim was to determine whether hybrids between Jacobaea aquatica and J. vulgaris also occurred in Austria, and if these hybrids could be responsible for the presumed increase of J. aquatica-like plants in this part of Europe. Furthermore, we tested if such hybrids showed an altered PA spectrum compared with parental species.

Methods: We used amplified fragment length polymorphisms (AFLPs) to analyse genetic diversity and structure, and gas chromatography–mass spectrometry (GC–MS) to identify PAs.

Results: We were able to identify genetically one hybrid population adjacent to a large J. aquatica population. The AFLP phenotypes of hybrids demonstrated a closer relationship to J. aquatica, suggesting frequent backcrossing. All hybrid individuals contained the same set of PAs as the parental species, but in differing amounts, plus four additional PAs, one of which may be novel.

Conclusions: Although hybridisation in Jacobaea is common, we were able to confirm only one hybrid population in Austria. Therefore, it seems unlikely that hybridisation plays a role in the presumed increase of J. aquatica in this area.     

New 4,5‐seco‐20(10→5)‐abeo‐Abietane Diterpenoids with Anti‐Inflammatory Activity from Isodon lophanthoides var. graciliflorus (Benth.) H.Hara

Three new 4,5‐seco‐20(10→5)‐abeo‐abietane diterpenoids, 16‐hydroxysalvilenone ( 1 ), 15‐hydroxysalprionin ( 2 ), and 11β,15‐dihydroxysalprionin‐12‐one ( 3 ), and nine known abietane diterpenoids, 4 – 12 , along with one known sempervirane diterpenoid, hispidanol A ( 13 ), were isolated from the aerial parts of Isodon lophanthoides var. graciliflorus. The structures of compounds 1 – 3 were determined on the basis of spectroscopic methods including extensive analysis of NMR and mass spectroscopic data. All diterpenoids were tested for their TNF‐α inhibitory effects on LPS‐induced RAW264.7 cells. Compound 9 (16‐acetoxyhorminone) was the most potent with an IC₅₀ value of 3.97±0.70 μm .     

Clinanthus microstephium,an Amaryllidaceae Species with Cholinesterase Inhibitor Alkaloids: Structure−Activity Analysis of Haemanthamine Skeleton Derivatives

Plants of the Amaryllidaceae family are well‐known (not only) for their ornamental value but also for the alkaloids that they produce. In this report, the first phytochemical study of Clinanthus genus was carried out. The chemical composition of alkaloid fractions from Clinanthus microstephium was analyzed by GC/MS and NMR. Seven known compounds belonging to three structural types of Amaryllidaceae alkaloids were identified. An epimeric mixture of a haemanthamine‐type compound (6‐hydroxymaritidine) was tested as an inhibitor against acetyl‐ and butyrylcholinesterase enzymes (AChE and BChE, respectively), two enzymes relevant in the treatment of Alzheimer's disease, with good results. Structure–activity relationships through molecular docking studies with this alkaloid and other structurally related compounds were discussed.     

Metabolite Profiling of Anti‐Addictive Alkaloids from Four Mexican Tabernaemontana Species and the Entheogenic African Shrub Tabernanthe iboga (Apocynaceae)

Ibogaine and other ibogan type alkaloids present anti‐addictive effects against several drugs of abuse and occur in different species of the Apocynaceae family. In this work, we used gas chromatography‐mass spectrometry (GC/MS) and principal component analysis (PCA) in order to compare the alkaloid profiles of the root and stem barks of four Mexican Tabernaemontana species with the root bark of the entheogenic African shrub Tabernanthe iboga. PCA demonstrated that separation between species could be attributed to quantitative differences of the major alkaloids, coronaridine, ibogamine, voacangine, and ibogaine. While T. iboga mainly presented high concentrations of ibogaine, Tabernaemontana samples either showed a predominance of voacangine and ibogaine, or coronaridine and ibogamine, respectively. The results illustrate the phytochemical proximity between both genera and confirm previous suggestions that Mexican Tabernaemontana species are viable sources of anti‐addictive compounds.     

Structure-activity relationships study of neolamellarin A and its analogues as hypoxia inducible factor-1 (HIF-1) inhibitors

The novel marine pyrrole alkaloid neolamellarin A derived from sponge has been shown to inhibit hypoxia-induced HIF-1 activity. In this work, we designed and synthesized neolamellarin A and its series of derivatives by a convergent synthetic strategy. The HIF-1 inhibitory activity and cytotoxicity of these compounds were evaluated in Hela cells by dual-luciferase reporter gene assay and MTT assay, respectively. The results showed that neolamellarin A 1 (IC₅₀ = 10.8 ± 1.0 μM) and derivative 2b (IC₅₀ = 11.9 ± 3.6 μM) had the best HIF-1 inhibitory activity and low cytotoxicity. Our SAR research focused on the effects of key regions aliphatic carbon chain length, aromatic ring substituents and C-7 substituent on biological activity, providing a basis for the subsequent research on the development of novel pyrrole alkaloids as HIF-1 inhibitors and design of small molecule probes for target protein identification.