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Bioorganic & Medicinal Chemistry Mar 2008The lipid-soluble veratrum alkaloids, veratridine and cevadine, are plant neurotoxins that are agonists of voltage-gated sodium channel. Their conformations in a...
The lipid-soluble veratrum alkaloids, veratridine and cevadine, are plant neurotoxins that are agonists of voltage-gated sodium channel. Their conformations in a hydrophobic environment were analyzed by NMR spectroscopy in solution phase chloroform at low temperatures. The conformations around the 3-carboxylic esters which is essential for their neurotoxicity, was completely different from the previously reported X-ray crystallographic structure. The carbonyl oxygen atom (O28) of the carboxylic ester forms a weak intramolecular hydrogen bond with the OH proton at C4 (4-OH) that loosely restricts the conformation of the 3-veratroyl ester in veratridine and the 3-angeloyl ester in cevadine. Methylation at C4 hydroxyl group of veratridine had much reduced its neurotoxic activity relating to voltage-gated sodium channel. The results suggested that the loose conformational restrictions of the carboxylic esters are important for neurotoxicity of the veratrum alkaloids.
Topics: Chloroform; Cold Temperature; Esters; Magnetic Resonance Spectroscopy; Molecular Conformation; Neurotoxins; Sodium Channel Agonists; Veratridine; Veratrine; Veratrum Alkaloids
PubMed: 18191403
DOI: 10.1016/j.bmc.2007.12.037 -
Bioorganic & Medicinal Chemistry Aug 2016Veratrum californicum, commonly referred to as corn lily or Californian false hellebore, grows in high mountain meadows and produces the steroidal alkaloid cyclopamine,...
Veratrum californicum, commonly referred to as corn lily or Californian false hellebore, grows in high mountain meadows and produces the steroidal alkaloid cyclopamine, a potent inhibitor of the Hedgehog (Hh) signaling pathway. The Hh pathway is a crucial regulator of many fundamental processes during vertebrate embryonic development. However, constitutive activation of the Hh pathway contributes to the progression of various cancers. In the present study, a direct correlation was made between the extraction efficiency for cyclopamine from root and rhizome by eight methods, and the associated biological activity in Shh-Light II cells using the Dual-Glo® Luciferase Assay System. Alkaloid recovery ranged from 0.39 to 8.03mg/g, with ethanol soak being determined to be the superior method for obtaining biologically active cyclopamine. Acidic ethanol and supercritical extractions yielded degraded or contaminated cyclopamine with lower antagonistic activity towards Hh signaling.
Topics: Biomass; Cell Line; Chromatography, High Pressure Liquid; Hedgehog Proteins; Signal Transduction; Veratrum; Veratrum Alkaloids
PubMed: 27338657
DOI: 10.1016/j.bmc.2016.06.017 -
The Journal of Pharmacology and... May 1953
Topics: Anura; Bufanolides; Cardiac Glycosides; Humans; Veratrum Alkaloids
PubMed: 13053418
DOI: No ID Found -
Experientia Mar 1954
Topics: Alkaloids; Cevanes; Humans; Veratrum Alkaloids
PubMed: 13161888
DOI: 10.1007/BF02158513 -
British Heart Journal Oct 1953
Topics: Hypertension; Protoveratrines; Veratrum Alkaloids
PubMed: 13093878
DOI: 10.1136/hrt.15.4.439 -
The Journal of Pharmacology and... Jan 1955
Mechanism of vasomotor action of Veratrum alkaloids: extravagal sites of action of veriloid, protoveratrine, germitrine, neogermitrine, germerine, veratridine and veratramine.
Topics: Blood Vessels; Germine Acetates; Humans; Protoveratrines; Veratridine; Veratrum Alkaloids
PubMed: 13234032
DOI: No ID Found -
Bioorganic & Medicinal Chemistry Sep 2010Since its discovery by C. Nüsslein-Volhard and E. F. Wieschaus, hedgehog (hh) signaling has come a long way. Today it is regarded as a key regulator in embryogenesis... (Review)
Review
Since its discovery by C. Nüsslein-Volhard and E. F. Wieschaus, hedgehog (hh) signaling has come a long way. Today it is regarded as a key regulator in embryogenesis where it governs processes like cell proliferation, differentiation, and tissue patterning. Furthermore, in adults it is involved in the maintenance of stem cells, and in tissue repair and regeneration. But hh signaling has a second-much darker-face: it plays an important role in several types of human cancers where it promotes growth and enables proliferation of tumor stem cells. The etiology of medulloblastoma and basal cell carcinoma is tightly linked to aberrant hh activity, but also cancers of the prostate, the pancreas, the colon, the breasts, rhabdomyosarcoma, and leukemia, are dependent on irregular hh activity. Recent clinical studies have shown that hh signaling can be the basis of an important new class of therapeutic agents with far-reaching implications in oncology. Thus, modulation of hh signaling by means of small molecules has emerged as a valuable tool in combating these hh-dependent cancers. Cyclopamine, a unique natural product with a fascinating history, was the first identified inhibitor of hh signaling and its story is closely linked to the progress in the whole field. In this review we will trace the story of cyclopamine, give an overview on the biological modes of hh signaling both in untransformed and malignant cells, and finally present potent modulators of the hh pathway-many of them already in clinical studies. For more than 30 years now the knowledge on hh signaling has grown steadily-an end to this development is far from being conceivable.
Topics: Antineoplastic Agents; Hedgehog Proteins; Humans; Neoplasms; Signal Transduction; Veratrum Alkaloids
PubMed: 20708941
DOI: 10.1016/j.bmc.2010.07.038 -
The Journal of Pharmacology and... Apr 1955
Topics: Animals; Dogs; Heart; Veratrum Alkaloids
PubMed: 14368514
DOI: No ID Found -
The Practitioner Feb 1953
Topics: Hypertension; Veratrum; Veratrum Alkaloids
PubMed: 13026647
DOI: No ID Found -
Prakticky Lekar Aug 1954
Topics: Veratrum Alkaloids
PubMed: 13194519
DOI: No ID Found