Ungeremine

Last updated
Ungeremine
Ungeremine.svg
Names
Preferred IUPAC name
2-Hydroxy-4,5-dihydro-10H-6λ5-[1,3]dioxolo[4,5-j]pyrrolo[3,2,1-de]phenanthridin-6-ylium
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
  • InChI=1S/C16H11NO3/c18-11-3-9-1-2-17-7-10-4-14-15(20-8-19-14)6-12(10)13(5-11)16(9)17/h3-7H,1-2,8H2/p+1
    Key: DFQOXFIPAAMFAU-UHFFFAOYSA-O
  • InChI=1/C16H11NO3/c18-11-3-9-1-2-17-7-10-4-14-15(20-8-19-14)6-12(10)13(5-11)16(9)17/h3-7H,1-2,8H2/p+1
    Key: DFQOXFIPAAMFAU-IKLDFBCSAD
  • C1C[N+]2=CC3=CC4=C(C=C3C5=CC(=CC1=C52)O)OCO4
Properties
C16H12NO3+1
Molar mass 266.275 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Ungeremine is a betaine-type alkaloid isolated from Nerine bowdenii [1] and related plants such as Pancratium maritimum . [2] Pharmacologically, it is of interest as an acetylcholinesterase inhibitor and accordingly as possibly relevant to Alzheimer's disease. [3] It also has been investigated as a bactericide. [2]

Related Research Articles

Cholinergic

Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin. Choline also prevents fat deposits in the liver and facilitates the movement of fats into cells.

Cholinesterase

In biochemistry, a cholinesterase or choline esterase is a family of esterases that lyses choline-based esters, several of which serve as neurotransmitters. Thus, it is either of two enzymes that catalyze the hydrolysis of these cholinergic neurotransmitters, such as breaking acetylcholine into choline and acetic acid. These reactions are necessary to allow a cholinergic neuron to return to its resting state after activation. For example, in muscle contraction, acetylcholine at a neuromuscular junction triggers a contraction; but for the muscle to relax afterward, rather than remaining locked in a tense state, the acetylcholine must be broken down by a choline esterase. The main type for that purpose is acetylcholinesterase ; it is found mainly in chemical synapses and red blood cell membranes. The other type is butyrylcholinesterase ; it is found mainly in the blood plasma.

Donepezil Medication used for dementia

Donepezil, sold as the trade name Aricept among others, is a medication used to treat Alzheimer's disease. It appears to result in a small benefit in mental function and ability to function. Use, however, has not been shown to change the progression of the disease. Treatment should be stopped if no benefit is seen. It is taken by mouth.

Tacrine

Tacrine is a centrally acting acetylcholinesterase inhibitor and indirect cholinergic agonist (parasympathomimetic). It was the first centrally acting cholinesterase inhibitor approved for the treatment of Alzheimer's disease, and was marketed under the trade name Cognex. Tacrine was first synthesised by Adrien Albert at the University of Sydney in 1949. It also acts as a histamine N-methyltransferase inhibitor.

Galantamine

Galantamine is used for the treatment of cognitive decline in mild to moderate Alzheimer's disease and various other memory impairments. It is an alkaloid that has been isolated from the bulbs and flowers of Galanthus nivalis, Galanthus caucasicus, Galanthus woronowii, and some other members of the family Amaryllidaceae, such as Narcissus (daffodil), Leucojum aestivum (snowflake), and Lycoris including Lycoris radiata. It can also be produced synthetically.

Memantine Medication used to treat moderate-to-severe Alzheimers disease

Memantine is a medication used to treat moderate-to-severe Alzheimer's disease. It is less preferred than acetylcholinesterase inhibitors such as donepezil. Treatment should only be continued if beneficial effects are seen. It is taken by mouth.

Huperzine A

Huperzine A is a naturally occurring sesquiterpene alkaloid compound found in the firmoss Huperzia serrata and in varying quantities in other food Huperzia species, including H. elmeri, H. carinat, and H. aqualupian. Huperzine A has been investigated as a treatment for neurological conditions such as Alzheimer's disease, but a meta-analysis of those studies concluded that they were of poor methodological quality and the findings should be interpreted with caution. Huperzine A inhibits the breakdown of the neurotransmitter acetylcholine by the enzyme acetylcholinesterase. It is commonly available over the counter as a nutrient supplement, and is marketed as a cognitive enhancer for improving memory and concentration.

Bulbocapnine Chemical compound

Bulbocapnine is an alkaloid found in Corydalis and Dicentra, genera of the plant family Fumariaceae which have caused the fatal poisoning of sheep and cattle. It has been shown to act as an acetylcholinesterase inhibitor, and inhibits biosynthesis of dopamine via inhibition of the enzyme tyrosine hydroxylase. Like apomorphine, it is reported to be an inhibitor of amyloid beta protein (Aβ) fiber formation, whose presence is a hallmark of Alzheimer's disease (AD). Bulbocapnine is thus a potential therapeutic under the amyloid hypothesis. According to the Dorlands Medical Dictionary, it "inhibits the reflex and motor activities of striated muscle. It has been used in the treatment of muscular tremors and vestibular nystagmus".

Metrifonate

Metrifonate (INN) or trichlorfon (USAN) is an irreversible organophosphate acetylcholinesterase inhibitor. It is a prodrug which is activated non-enzymatically into the active agent dichlorvos.

Acetylcholinesterase A gene or the protein it encodes in various Animalia including humans

Acetylcholinesterase, also known as AChE or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme that catalyzes the breakdown of acetylcholine and of some other choline esters that function as neurotransmitters. AChE is found at mainly neuromuscular junctions and in chemical synapses of the cholinergic type, where its activity serves to terminate synaptic transmission. It belongs to carboxylesterase family of enzymes. It is the primary target of inhibition by organophosphorus compounds such as nerve agents and pesticides.

Alzheimers disease Progressive, neurodegenerative disease characterized by memory loss

Alzheimer's disease (AD), also referred to simply as Alzheimer's, is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation, mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years.

Acetylcholinesterase inhibitor

Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level and duration of action of acetylcholine in the central nervous system, autonomic ganglia and neuromuscular junctions, which are rich in acetylcholine receptors. Acetylcholinesterase inhibitors are one of two types of cholinesterase inhibitors; the other being butyryl-cholinesterase inhibitors. Acetylcholinesterase is the primary member of the cholinesterase enzyme family.

Cholinesterase inhibitor Chemicals which prevent breakdown of acetylcholine and butyrylcholine

Cholinesterase inhibitors (ChEIs), also known as anti-cholinesterase, are chemicals that prevent the breakdown of the neurotransmitter acetylcholine or butyrylcholine. This increases the amount of the acetylcholine or butyrylcholine in the synaptic cleft that can bind to muscarinic receptors, nicotinic receptors and others. This group of inhibitors is divided into two subgroups, acetylcholinesterase inhibitors (AChEIs) and butyrylcholinesterase inhibitors (BChEIs).

Tenuazonic acid Chemical compound

Tenuazonic acid is a mycotoxin produced by Alternaria species. It is a powerful eukaryotic protein synthesis inhibitor. It is a tetrameric acid that is ubiquitous in biological environments and prevents the release of newly synthesized protein from the ribosome. Its toxicity is the highest among all Alternaria mycotoxins and has both phytotoxic and cytotoxic properties. In 1991 Tenuazonic acid was reported to inhibit skin tumor promotion in mice.

Ladostigil

Ladostigil (TV-3,326) is a novel neuroprotective agent being investigated for the treatment of neurodegenerative disorders like Alzheimer's disease, Lewy body disease, and Parkinson's disease. It acts as a reversible acetylcholinesterase and butyrylcholinesterase inhibitor, and an irreversible monoamine oxidase B inhibitor, and combines the mechanisms of action of older drugs like rivastigmine and rasagiline into a single molecule. In addition to its neuroprotective properties, ladostigil enhances the expression of neurotrophic factors like GDNF and BDNF, and may be capable of reversing some of the damage seen in neurodegenerative diseases via the induction of neurogenesis. Ladostigil also has antidepressant effects, and may be useful for treating comorbid depression and anxiety often seen in such diseases as well.

<i>Nerine bowdenii</i> Species of flowering plant

Nerine bowdenii is a species of flowering plant in the family Amaryllidaceae. It is an herbaceous bulbous perennial, growing to 45 cm (18 in) tall by 8 cm (3 in), with strap-shaped leaves and large umbels of lily-like pink flowers in late summer and autumn. The common names of the species are Cornish lily, Cape flower, Guernsey lily, and Bowden lily. However, it is neither a true lily nor from Cornwall or Guernsey, but originates from South Africa. Confusingly the name “Guernsey lily” is also applied to a related species, Nerine sarniensis.

Rivastigmine

Rivastigmine is a cholinesterase inhibitor used for the treatment of mild to moderate Alzheimer's disease and Parkinson's. The drug can be administered orally or via a transdermal patch; the latter form reduces the prevalence of side effects, which typically include nausea and vomiting.

Methanesulfonyl fluoride (MSF) has long been known to be a potent inhibitor of acetylcholinesterase (AChE), the enzyme that regulates acetylcholine, an important neurotransmitter in both the central and peripheral nervous systems.

Phenserine

Phenserine is a synthetic drug which has been investigated as a medication to treat Alzheimer's disease (AD), as the drug exhibits neuroprotective and neurotrophic effects.

Huprine X

Huprine X is a synthetic cholinergic compound developed as a hybrid between the natural product Huperzine A and the synthetic drug tacrine. It is one of the most potent reversible inhibitors of acetylcholinesterase known, with a binding affinity of 0.026nM, as well as showing direct agonist activity at both nicotinic and muscarinic acetylcholine receptors. In animal studies it has nootropic and neuroprotective effects, and is used in research into Alzheimer's disease, and although huprine X itself has not been researched for medical use in humans, a large family of related derivatives have been developed.

References

  1. Rhee, I. K.; Appels, N; Hofte, B; Karabatak, B; Erkelens, C; Stark, L. M.; Flippin, L. A.; Verpoorte, R (2004). "Isolation of the acetylcholinesterase inhibitor ungeremine from Nerine bowdenii by preparative HPLC coupled on-line to a flow assay system". Biological & Pharmaceutical Bulletin. 27 (11): 1804–9. doi: 10.1248/bpb.27.1804 . PMID   15516727.
  2. 1 2 Schrader, Kevin K.; Avolio, Fabiana; Andolfi, Anna; Cimmino, Alessio; Evidente, Antonio (2013). "Ungeremine and Its Hemisynthesized Analogues as Bactericides against Flavobacterium columnare". Journal of Agricultural and Food Chemistry. 61 (6): 1179–83. doi:10.1021/jf304586j. PMID   23331165.
  3. Murray, Ana; Faraoni, Maria; Castro, María; Alza, Natalia; Cavallaro, Valeria (2013). "Natural AChE Inhibitors from Plants and their Contribution to Alzheimer's Disease Therapy". Current Neuropharmacology. 11 (4): 388–413. doi:10.2174/1570159X11311040004. PMC   3744903 . PMID   24381530.