Wednesday, 14 June 2017

Phytotoxin kháng L1210

Inhibitory effects of phaseolotoxin on proliferation of leukemia cells HL ...

Phytotoxin kháng L1210

From Wikipedia, the free encyclopedia
Phytotoxin is an umbrella term that refers to substances (known as phytotoxic substances) that are inhibitory to the growth of or poisonous to plants. Phytotoxic substances may result from human activity, as with herbicides, or they may be produced by plants, by microorganisms, or by naturally occurring chemical reactions.[1] A good soil will protect plants from toxic concentrations of such substances by ventilating gases, decomposing or adsorbing organic toxins, or suppressing toxin-producing organisms.
The term is also sometimes used, on the contrary, to describe toxic chemicals produced by plants themselves, which function as defensive agents against their predators. Most examples pertaining to this definition of phytotoxin are members of various classes of secondary metabolites, including alkaloidsterpenes, and especially phenolics, though not all such compounds are toxic or serve defensive purposes.[2] Phytotoxins may also be toxic to humans.[3][4]

Toxins produced by plants[edit]

Alkaloids[edit]

Alkaloids are derived from amino acids, and contain nitrogen.[5] They are medically important by interfering with components of the nervous system affecting membrane transportprotein synthesis, and enzyme activities. They generally have a bitter taste. Alkaloids usually end in -ine (caffeinenicotinecocainemorphineephedrine).

Terpenes[edit]

Terpenes are made of water-insoluble lipids, and synthesized from acetyl-CoA or basic intermediates of glycolysis[6] They often end in -ol (menthol) and comprise the majority of plant essential oils.
  • Monoterpenes are found in gymnosperms and collect in the resin ducts and maybe released after an insect begins to feed to attract the insect's natural enemies.
  • Sesquiterpenes are bitter tasting to humans and are found on glandular hairs or subdermal pigments.
  • Diterpenes are contained in resin and block and deter insect feeding. Taxol, an important anticancer drug is found in this group.
  • Triterpenes mimic the insect molting hormone ecdysone, disrupting molting and development and is often lethal. They are usually found in citrus fruit, and produce a bitter substance called limonoid that deters insect feeding.
  • Glycosides are made of one or more sugars combined with a non-sugar like aglycone, which usually determines the level of toxicityCyanogenic glycosides are found in many plant seeds like cherriesapples, and plums. Cyanogenic glycosides produce cyanide and are extremely poisonous.Cardenolides have a bitter taste and influence NA+/K+ activated ATPases in human heart, they may slow or strengthen the heart rate. Saponins have lipid- and water-soluble components with detergent properties. Saponins form complexes with sterols and interfere with their uptake.

Phenolics[edit]

Phenolics are made of a hydroxyl group bonded to an aromatic hydrocarbonFuranocoumarin is a phenolic and is non-toxic until activated by light. Furanocoumarin blocks the transcription and repair of DNATannins are another group of phenolics important in tanning leatherLignins, also a group of phenolics, are the most common compounds on Earth, and help conduct water in plant stems and fill spaces in the cell.

Substances toxic to plants[edit]

Herbicides[edit]

Herbicides usually interfere with plant growth and often imitate plant hormones.
  • ACCase Inhibitors kill grasses and inhibit the first step in lipid synthesis, acetyl-CoA carboxylase, thus affecting cell membrane production in the meristems. They do not affect dicots plants.[7]
  • ALS Inhibitors affect grasses and dicots by inhibiting the first step in some amino acid synthesis, acetolactate synthesis. The plants are slowly starved of theses amino acids and eventually DNA synthesis stops.
  • ESPS Inhibitors affect grasses and dicots by inhibiting the first step in the synthesis of tryptophanphenylalanine and tyrosine, enolpyruvylshikimate 3-phosphate synthase enzyme.
  • Photosystem II Inhibitors reduce the electron flow from water to NADPH2+ causing electrons to accumulate on chlorophyll molecules and excess oxidation to occur. The plant will eventually die.
  • Synthetic Auxin mimics plant hormones and can affect the plant cell membrane.

Bacterial phytotoxins[edit]

  • Tabtoxin is produced by Pseudomonas syringae pv. tabaci that may cause toxic concentrations of ammonia to build up. This buildup of ammonia causes leaf chlorosis.[8]
  • Glycopeptides are produced by a number of bacteria and have been indicated in disease development.[8] A glycopeptide from Corynebacterium sepedonicumcauses rapid wilt and marginal necrosis. A toxin from Corynebacterium insidiosum causes plugging of the plant stem interfering with water movement between cells.[8] Amylovorin is a polysaccharide from Erwinia amylovora and causes wilting in rosaceous plants. A polysaccharide from Xanthomonas campestris obstructs water flow through phloem causing black rot in cabbage.
  • Phaseolotoxin is a modified tripeptide [Nδ-(N′-sulfodiaminophosphinyl)-ornithyl-alanyl-homoarginine] produced by certains strains of Pseudomonas syringae pv. phaseolicolaPseudomonas syringae pv. actinidiae and strain Pseudomonas syringae pv. syringae CFBP 3388.[9][10][11] Phaseolotoxin is a reversible inhibitor of the enzyme ornithine carbamoyltransferase (OCTase; EC 2.1.3.3), which catalyzes the formation of citrulline from ornithine and carbamoylphosphate in the arginine biosynthetic pathway. Phaseolotoxin is an effective inhibitor of OCTase activity from plant, mammalian, and bacterial sources and causes a phenotypic requirement for arginine. Additionally, phaseolotoxin inhibits the enzyme ornithine decarboxylase (EC 4.1.1.17), which is involved in the biosynthesis of polyamines.[12]
  • Rhizobiotoxine, produced by Rhizobium japonicum, causes the root nodules of some soy bean plants to become chlorotic.

Omacetaxine mepesuccinate kháng L1210

Two homoharringtonine resistant leukemic cell lines(K562 HHT and ...

Homoharringtonine  (Omacetaxine mepesuccinate) kháng L1210

From Wikipedia, the free encyclopedia
  (Redirected from Homoharringtonine)
Omacetaxine mepesuccinate
Omacetaxine mepesuccinate.svg
Omacetaxine mepesuccinate3DS.svg
Clinical data
Trade namesSynribo
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • US: D (Evidence of risk)
    Routes of
    administration
    Subcutaneousintravenous infusion
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Protein binding50%
    MetabolismMostly via plasma esterases
    Biological half-life6 hours
    ExcretionUrine (≤15% unchanged)
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    ChemSpider
    UNII
    KEGG
    ChEBI
    ECHA InfoCard100.164.439
    Chemical and physical data
    FormulaC29H39NO9
    Molar mass545.62 g/mol
    3D model (Jmol)
    Omacetaxine mepesuccinate (INN, trade names Synribo or Myelostat ), formerly named as homoharringtonine or HHT, is a pharmaceutical drug substance that is indicated for treatment of chronic myeloid leukemia (CML). It is a natural product first discovered in Cephalotaxus harringtonii, now manufactured by hemi-synthesis. It was approved by the US FDA in October 2012 for the treatment of adult patients with CML with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs).[1]

    Medical uses[edit]

    Omacetaxine/homoharringtonine is indicated for use as a treatment for patients with chronic myeloid leukaemia who are resistant or intolerant of tyrosine kinase inhibitors.[2][3][4]
    In June 2009, results of a long-term open label Phase II study were published, which investigated the use of omacetaxine infusions in CML patients. After twelve months of treatment, about one third of patients showed a cytogenetic response.[5] A study in patients who had failed imatinib and who had the drug resistant T315I mutation achieved cytogenetic response in 28% of patients and hematologic response in 80% of patients, according to preliminary data.[6]
    Phase I studies including a small number of patients have shown benefit in treating myelodysplastic syndrome(MDS, 25 patients)[7] and acute myelogenous leukaemia (AML, 76 patients).[8] Patients with solid tumors did not benefit from omacetaxine.[9]

    Adverse effects[edit]

    By frequency:[1][2]
    Very common (>10% frequency):
    • Diarrhoea
    • Myelosuppression
    • Injection site reactions
    • Nausea
    • Fatigue
    • Fever
    • Muscle weakness
    • Joint pain
    • Headache
    • Cough
    • Hair loss
    • Constipation
    • Nosebleeds
    • Upper abdominal pain
    • Pain in the extremities
    • Oedema
    • Vomiting
    • Back pain
    • Hyperglycemia, sometimes extreme
    • Gout
    • Rash
    • Insomnia
    Common (1-10% frequency):
    • Seizures
    • Haemorrhage
     Myelosuppression, including: thrombocytopeniaanaemianeutropenia and lymphopenia, in descending order of frequency.

    Mechanism of action[edit]

    Omacetaxine is a protein translation inhibitor. It inhibits protein translation by preventing the initial elongation step of protein synthesis. It interacts with the ribosomal A-site and prevents the correct positioning of amino acid side chains of incoming aminoacyl-tRNAs. Omacetaxine acts only on the initial step of protein translation and does not inhibit protein synthesis from mRNAs that have already commenced translation.[10]