Visnagin

Last updated
Visnagin
Visnagin.svg
Names
Preferred IUPAC name
4-Methoxy-7-methyl-5H-furo[3,2-g][1]benzopyran-5-one [1]
Other names
Visnacorin; Khella; Desmethoxykhellin; 5-Methoxy-2-methylfuranochromone; 5-Methoxy-2-methyl-6,7-furanochrome
Identifiers
3D model (JSmol)
5-19-06-00030
ChEBI
ChemSpider
ECHA InfoCard 100.001.301 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 201-430-3
234955
KEGG
PubChem CID
RTECS number
  • LV1420000
UNII
  • C12=C(C3=C(C=C1OC(=CC2=O)C)OC=C3)OC
Properties
C13H10O4
Molar mass 230.219 g·mol−1
AppearanceSolid
Melting point 144 to 145 °C (291 to 293 °F; 417 to 418 K)
soluble
Solubility ethanol
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
Harmful by ingestion
GHS labelling:
GHS-pictogram-exclam.svg
Warning
NFPA 704 (fire diamond)
NFPA 704.svgHealth 1: Exposure would cause irritation but only minor residual injury. E.g. turpentineFlammability 0: Will not burn. E.g. waterInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
1
0
0
Lethal dose or concentration (LD, LC):
832 mg/kg (oral, rat)
Safety data sheet (SDS) Sigma-Aldrich MSDS
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Visnagin is an organic chemical compound with the molecular formula C 13 H 10 O 4 It is a furanochromone, a compound derivative of chromone (1,4-benzopyrone) and furan.

Contents

History

Visnaga daucoides , the main source for visnagin, has been used in traditional medicine in the Middle East to ease urinary tract pain associated with kidney stones and to promote stone passage. [2]

Occurrences

Visnagin naturally occurs in Visnaga daucoides, a species of flowering plant in the carrot family known by many common names, including bisnaga, toothpickweed, and khella. Visnagin-containing khella seeds are usually found mainly in Middle East countries such as Egypt and Turkey and also in Northern African countries such as Morocco. Visnagin can be extracted directly from khella seeds.

Synthesis

Modified synthesis of the naturally occurring visnagin is reported. Starting from phloroghrcin aldehyde, and building on the 2-methyl-y-pyrone, 2-methyl-5,7-dihydroxy-dfo-yl-chromone was obtained. Construction of the furan moiety was realized by a conventional method through the 7-carboxymethoxy ether giving S-norvisnagin which can be methylated to visnagin. [3]

Reactions

Condensation

Visnagin analogs can be synthesized through the condensation of visnagone with esters and sodium. This leads to the product of 2-ethyl, 2-(3'-pyridyl) visnagin analog (50c). [4] Visnagin Reaction.png [4]

Oligomerization

Visnagin molecules can go over an oligomerization to form a chain of visnagin molecules. [5]

Visnagin olygomerization reaction Visnagin olygomer.png
Visnagin olygomerization reaction

Animal study

Visnagin has biological activity in animal models as a vasodilator and reduces blood pressure by inhibiting calcium influx into the cell. [6] In rats, visnagin prevents the formation of kidney stones by prolonging the induction time of nucleation of crystals. [7] On December 8, 2014, it was reported that "visnagin protects against doxorubicin-induced cardiomyopathy through modulation of mitochondrial malate dehydrogenase." [8] In another scientific study, it was reported that visnagin treatment reduced ischemia-reperfusion associated testicular injury in urological interventions. [9]

Related Research Articles

<span class="mw-page-title-main">Succinic acid</span> Dicarboxylic acid

Succinic acid is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into fumarate by the enzyme succinate dehydrogenase in complex 2 of the electron transport chain which is involved in making ATP, and as a signaling molecule reflecting the cellular metabolic state.

<span class="mw-page-title-main">Protecting group</span> Group of atoms introduced into a compound to prevent subsequent reactions

A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis.

Furan is a heterocyclic organic compound, consisting of a five-membered aromatic ring with four carbon atoms and one oxygen atom. Chemical compounds containing such rings are also referred to as furans.

<span class="mw-page-title-main">Cromoglicic acid</span> Chemical compound

Cromoglicic acid (INN)—also referred to as cromolyn (USAN), cromoglycate, or cromoglicate—is traditionally described as a mast cell stabilizer, and is commonly marketed as the sodium salt sodium cromoglicate or cromolyn sodium. This drug prevents the release of inflammatory chemicals such as histamine from mast cells.

<span class="mw-page-title-main">Flavin mononucleotide</span> Chemical compound

Flavin mononucleotide (FMN), or riboflavin-5′-phosphate, is a biomolecule produced from riboflavin (vitamin B2) by the enzyme riboflavin kinase and functions as the prosthetic group of various oxidoreductases, including NADH dehydrogenase, as well as cofactor in biological blue-light photo receptors. During the catalytic cycle, a reversible interconversion of the oxidized (FMN), semiquinone (FMNH), and reduced (FMNH2) forms occurs in the various oxidoreductases. FMN is a stronger oxidizing agent than NAD and is particularly useful because it can take part in both one- and two-electron transfers. In its role as blue-light photo receptor, (oxidized) FMN stands out from the 'conventional' photo receptors as the signaling state and not an E/Z isomerization.

The Étard reaction is a chemical reaction that involves the direct oxidation of an aromatic or heterocyclic bound methyl group to an aldehyde using chromyl chloride. For example, toluene can be oxidized to benzaldehyde.

<span class="mw-page-title-main">Khellin</span> Chemical compound

Khellin has been used as an herbal folk medicine, with use in the Mediterranean dating back to Ancient Egypt, to treat a variety of maladies including: renal colic, kidney stones, coronary disease, bronchial asthma, vitiligo, and psoriasis. It is a major constituent of the plant Visnaga daucoides, also known as Ammi visnaga and as bishop's weed. Once purified, khellin exists as colorless, odorless, bitter-tasting needle-shaped crystals and is classified as a gamma-pyrone, a furanochromone derivative. In the early 20th century, researchers searched for khellin analogs with lower toxicity and better efficacy. A number of drugs were discovered through this research, such as amiodarone and cromolyn sodium, which are used in current medical practice. Efloxate is also mentioned as analog.

<span class="mw-page-title-main">Malate dehydrogenase 2</span> Enzyme that oxidizes malate to oxaloacetate in Krebs cycle

Malate dehydrogenase, mitochondrial also known as malate dehydrogenase 2 is an enzyme that in humans is encoded by the MDH2 gene.

<span class="mw-page-title-main">Achmatowicz reaction</span> Organic synthesis

The Achmatowicz reaction, also known as the Achmatowicz rearrangement, is an organic synthesis in which a furan is converted to a dihydropyran. In the original publication by the Polish Chemist Osman Achmatowicz Jr. in 1971 furfuryl alcohol is reacted with bromine in methanol to 2,5-dimethoxy-2,5-dihydrofuran which rearranges to the dihydropyran with dilute sulfuric acid. Additional reaction steps, alcohol protection with methyl orthoformate and boron trifluoride) and then ketone reduction with sodium borohydride produce an intermediate from which many monosaccharides can be synthesised.

<i>Visnaga daucoides</i> Species of plant

Visnaga daucoides is a species of flowering plant in the carrot family known by many common names, including toothpick-plant, toothpickweed, bisnaga, khella, or sometimes bishop's weed. It is native to Europe, Asia, and North Africa, but it can be found throughout the world as an introduced species.

<span class="mw-page-title-main">Furanochromone</span> Chemical compound

Furanochromone is a chemical compound which is a derivative of chromone (1,4-benzopyrone) and furan.

<span class="mw-page-title-main">Coffee furanone</span> Chemical compound

Coffee furanone (2-methyltetrahydrofuran-3-one) is a pleasant smelling liquid furan derivative which is a volatile constituent of the aroma complex of roasted coffee. Coffee furanone is less odorous than furfuryl mercaptan, which with an odor threshold of 0.005 ppb was the first high impact aroma chemical, but has a very pleasant sweet caramel character, with some nuttiness.

Ampelopsin may refer to:

<span class="mw-page-title-main">Lavendamycin</span> Chemical compound

Lavendamycin is a naturally occurring chemical compound discovered in fermentation broth of the soil bacterium Streptomyces lavendulae. Lavendamycin has antibiotic properties and anti-proliferative effects against several cancer cell lines. The use of lavendamycin as a cytotoxic agent in cancer therapy failed due to poor water solubility and non-specific cytotoxicity. The study of lavendamycin-based analogs designed to overcome these liabilities has been an area of research.

<span class="mw-page-title-main">17α-Methyl-19-norprogesterone</span> Chemical compound

17α-Methyl-19-norprogesterone, also known as 17α-methyl-19-norpregn-4-ene-3,20-dione, is a progestin which was never marketed. It is a derivative of progesterone, and is the combined derivative of 17α-methylprogesterone and 19-norprogesterone. The drug is the parent compound of a subgroup of the 19-norprogesterone group of progestins, which includes demegestone, promegestone, and trimegestone.

Kidney ischemia is a disease with a high morbidity and mortality rate. Blood vessels shrink and undergo apoptosis which results in poor blood flow in the kidneys. More complications happen when failure of the kidney functions result in toxicity in various parts of the body which may cause septic shock, hypovolemia, and a need for surgery. What causes kidney ischemia is not entirely known, but several pathophysiology relating to this disease have been elucidated. Possible causes of kidney ischemia include the activation of IL-17C and hypoxia due to surgery or transplant. Several signs and symptoms include injury to the microvascular endothelium, apoptosis of kidney cells due to overstress in the endoplasmic reticulum, dysfunctions of the mitochondria, autophagy, inflammation of the kidneys, and maladaptive repair.

The Griesbaum coozonolysis is a name reaction in organic chemistry that allows for the preparation of tetrasubstituted ozonides (1,2,4-trioxolanes) by the reaction of O-methyl oximes with a carbonyl compound in the presence of ozone. Contrary to their usual roles as intermediates in ozonolysis and other oxidative alkene cleavage reactions, 1,2,4-trioxolanes are relatively stable compounds and are isolable.

2-Methoxyethoxymethyl chloride is an organic compound with formula CH3OCH2CH2OCH2Cl. A colorless liquid, it is classified as a chloroalkyl ether. It is used as an alkylating agent. In organic synthesis, it is used for introducing the methoxyethoxy ether (MEM) protecting group. MEM protecting groups are generally preferred to methoxymethyl (MOM) protecting groups, both in terms of formation and removal.

Jiro Tsuji was a Japanese chemist, notable for his discovery of organometallic reactions, including the Tsuji-Trost reaction, the Tsuji-Wilkinson decarbonylation, and the Tsuji-Wacker reaction.

<span class="mw-page-title-main">4,6-Dimethyldibenzothiophene</span> Chemical compound


4,6-Dimethyldibenzothiophene is an organosulfur compound with the formula (C6H3CH3)2S. It is one of several dimethyl derivatives of benzothiophene. The compound is of particular interest as an organosulfur contaminant in petroleum that is recalcitrant. Both methyl groups shield the sulfur center from desulfurization.

References

  1. Visnacorin, ChemSpider
  2. Haug, Karin G.; Weber, Benjamin; Hochhaus, Guenther; Butterweck, Veronika (2012). "Nonlinear pharmacokinetics of visnagin in rats after intravenous bolus administration". European Journal of Pharmaceutical Sciences. 45 (1–2): 79–89. doi:10.1016/j.ejps.2011.10.023. PMID   22085634. Ammi visnaga L. (syn. Khella, Apiaceae) fruit preparations, such as tea prepared from crushed or powdered seeds, have traditionally been used in the Middle East to ease urinary tract pain associated with kidney stones and to promote stone passage (Gunaydin and Beyazit, 2004).
  3. Badawi, M.M.; Fayez, M.B.E. (1965). "Natural chromones—I". Tetrahedron. 21 (10): 2925. doi:10.1016/S0040-4020(01)98378-4.
  4. 1 2 Mustafa, Ahmed (2009-09-15). The Chemistry of Heterocyclic Compounds, Furopyrans and Furopyrones. John Wiley & Sons. ISBN   9780470188354.
  5. Pradhan, Padmanava; Banerji, Asoke (1998). "Novel cyclobutane fused furochromone oligomers from the seeds of Pimpinella monoica Dalz". Tetrahedron. 54 (48): 14541. doi:10.1016/S0040-4020(98)00913-2.
  6. Lee, Jin-Koo; Jung, Jun-Sub; Park, Sang-Hee; Park, Soo-Hyun; Sim, Yun-Beom; Kim, Seon-Mi; Ha, Tal-Soo; Suh, Hong-Won (2010). "Anti-inflammatory effect of visnagin in lipopolysaccharide-stimulated BV-2 microglial cells". Archives of Pharmacal Research. 33 (11): 1843–50. doi:10.1007/s12272-010-1117-1. PMID   21116788. S2CID   22168754.
  7. Abdel-Aal, E.A.; Daosukho, S.; El-Shall, H. (2009). "Effect of supersaturation ratio and Khella extract on nucleation and morphology of kidney stones". Journal of Crystal Growth. 311 (9): 2673. Bibcode:2009JCrGr.311.2673A. doi:10.1016/j.jcrysgro.2009.02.027.
  8. Liu, Y.; Asnani, A.; Zou, L.; Bentley, V. L.; Yu, M.; Wang, Y.; Dellaire, G.; Sarkar, K. S.; Dai, M.; Chen, H. H.; Sosnovik, D. E.; Shin, J. T.; Haber, D. A.; Berman, J. N.; Chao, W.; Peterson, R. T. (10 December 2014). "Visnagin protects against doxorubicin-induced cardiomyopathy through modulation of mitochondrial malate dehydrogenase". Science Translational Medicine. 6 (266): 266ra170. doi:10.1126/scitranslmed.3010189. PMC   4360984 . PMID   25504881.
  9. Sağır, S., Şeker, U., Pekince Özener, M., Yüksel, M., & Demir, M. (2023). "Oxidative stress, apoptosis, inflammation, and proliferation modulator function of visnagin provide gonadoprotective activity in testicular ischemia-reperfusion injury". European Review for Medical and Pharmacological Sciences. 27 (20): 9968-9977| doi: 10.26355/eurrev_202310_34176