Sunday, 11 June 2017

Falcarinol hợp chất kháng HL60

Induction of Apoptosis in Human Promyelocytic Leukemia HL60 Cells ...

Falcarinol hợp chất kháng HL60

From Wikipedia, the free encyclopedia
Falcarinol
Falcarinol.svg
Names
IUPAC name
(3S,9Z)-Heptadeca-1,9-diene-4,6-diyn-3-ol
Other names
Carotatoxin, panaxynol
Identifiers
3D model (JSmol)
ChemSpider
KEGG
PubChem CID
Properties
C17H24O
Molar mass244.38 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
 verify (what is Yes ?)
Infobox references
Falcarinol (also known as carotatoxin or panaxynol) is a natural pesticide and fatty alcohol found in carrots (Daucus carota), red ginseng (Panax ginseng) and ivy. In carrots, it occurs in a concentration of approximately 2 mg/kg.[1][2] As a toxin, it protects roots from fungal diseases, such as liquorice rot that causes black spots on the roots during storage. The compound requires the freezing condition to maintain well because it is sensitive to light and heat.
Falcarinol was also credited for helping to prevent colon cancer.[3]

Chemistry[edit]

Falcarinol is a polyyne with two carbon-carbon triple bonds and two double bonds.[4] The double bond at the carbon 9 position has cis stereochemistry was introduced by the desaturation, which requires oxygen and NADPH (or NADH) cofactors, creates a bend in the molecule that prevent fatty acid from solidifying in oils and cellular membranes.
It is structurally related to the oenanthotoxin and cicutoxin.

Biological effects[edit]

Falcarinol is an irritant that can cause allergic reactions and contact dermatitis.[5] It was shown that falcarinol acts as a covalent cannabinoid receptor type 1 inverse agonist and blocks the effect of anandamide in keratinocytes, leading to pro-allergic effects in human skin.[6]
Preliminary research in animal models suggest that falcarinol may have a protective effect against certain types of cancer. Laboratory rats fed a diet containing raw carrots or isolated falcarinol were a third less likely to develop full-scale tumors induced by azoxymethane than those in a control group.[7][8][9]
Normal consumption of carrots doesn't cause any toxic effect in humans. However, when falcarinol is delivered in high doses to laboratory animals, it causes neurotoxicological problems.[10]

Biosynthesis[edit]

Starting with oleic acid (1), which possesses a cis double bond at the carbon 9 position from desaturation and a bound of phospholipids (-PL), a bifunctional desaturase/acetylnase system occurred with oxygen (a) to introduce the second cis double bond at the carbon 12 position to form linoleic acid (2). This step was then repeated to turn the cis double bond at the carbon 12 position into a triple bond (also called acetylenic bond) to form crepenynic acid (3). Crepenynic acid was reacted with oxygen (b) to form a second cis double bond at the carbon 14 position (conjugated position) leading to the formation of dehydrocrepenynic acid (4). Allylic isomerization (c) was responsible for the changes from the cis double bond at the carbon 14 position into the triple bond (5) and formation of the more favored trans (E) double bond at the carbon 17 position (6). Finally, after forming the intermediate (7) by decarboxylation (d), falcarinol (8) was produced by hydrolyzation (e) at the carbon 16 position that introduced the R conformation to the system.[11]
Posted by at No comments:

Curcumin hợp chất kháng HL60

Curcumin induces apoptosis of multidrug-resistant human leukemia ...

Curcumin hợp chất kháng HL60

From Wikipedia, the free encyclopedia
Curcumin
Skeletal formula
Enol form
Skeletal formula
Keto form
Ball-and-stick model
Ball-and-stick model
Names
Pronunciation/ˈkɜːrkjᵿmɪn/
Preferred IUPAC name
(1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione
Other names
(1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione
Diferuloylmethane
Curcumin I
C.I. 75300
Natural Yellow 3
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
E numberE100 (colours)
PubChem CID
UNII
Properties
C21H20O6
Molar mass368.39 g·mol−1
AppearanceBright yellow-orange powder
Melting point183 °C (361 °F; 456 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
 verify (what is Yes ?)
Infobox references
Not to be confused with Curculin.
Curcumin is a bright yellow chemical produced by some plants. It is the principal curcuminoid of turmeric (Curcuma longa), a member of the ginger family (Zingiberaceae). It is sold as an herbal supplement, cosmetics ingredient, food flavoring, and food coloring.[1] As a food additive, its E number is E100.[2]
It was first isolated in 1815 when Vogel and Pierre Joseph Pelletier reported the isolation of a "yellow coloring-matter" from the rhizomes of turmeric and named it curcumin.[3] Although curcumin has been used historically in Ayurvedic medicine,[4] its potential for medicinal properties remains unproven and is questionable as a therapy when used orally.[5][6][7]
Chemically, curcumin is a diarylheptanoid, belonging to the group of curcuminoids, which are natural phenols responsible for turmeric's yellow color. It is a tautomeric compound existing in enolic form in organic solvents and as a keto form in water.[8]

Applications[edit]

The most common applications are as a dietary supplement, in cosmetics, as a food coloring, and as flavoring for foods such as turmeric-flavored beverages (Japan).[1]

Curcumin
Annual sales of curcumin have increased since 2012, largely due to an increase in its popularity as a dietary supplement.[1] It is increasingly popular in skincare products that are marketed as containing natural ingredients or dyes, especially in Asia.[1] The largest market is in North America, where sales exceeded US$20 million in 2014.[1]

Chemistry[edit]

Curcumin incorporates several functional groups whose structure was first identified in 1910.[9] The aromatic ring systems, which are phenols, are connected by two α,β-unsaturated carbonyl groups. The diketones form stable enols and are readily deprotonated to form enolates; the α,β-unsaturated carbonyl group is a good Michael acceptor and undergoes nucleophilic addition.
Curcumin is used as a complexometric indicator for boron.[10] It reacts with boric acid to form a red-colored compound, rosocyanine.

Biosynthesis[edit]

The biosynthetic route of curcumin is uncertain. In 1973, Roughly and Whiting proposed two mechanisms for curcumin biosynthesis. The first mechanism involves a chain extension reaction by cinnamic acid and 5 malonyl-CoA molecules that eventually arylized into a curcuminoid. The second mechanism involves two cinnamate units coupled together by malonyl-CoA. Both use cinnamic acid as their starting point, which is derived from the amino acid phenylalanine.[11]
Plant biosyntheses starting with cinnamic acid is rare compared to the more common p-coumaric acid.[11] Only a few identified compounds, such as anigorufone and pinosylvin, build from cinnamic acid.[12][13]
Curcumin biosynthesis diagram
malonyl-CoA (5)
Biosynthetic pathway of curcumin in Curcuma longa.[11]

Research[edit]

In vitro, curcumin exhibits numerous interference properties which may lead to misinterpretation of results.[5][6]
Although curcumin has been assessed in numerous laboratory and clinical studies, it has no medical uses established by well-designed clinical research.[14] According to a 2017 review of over 120 studies, curcumin has not been successful in any clinical trial, leading the authors to conclude that "curcumin is an unstable, reactive, non-bioavailable compound and, therefore, a highly improbable lead".[5]
Cancer studies using curcumin conducted by Bharat Aggarwal, formerly a researcher at the MD Anderson Cancer Center, were deemed fraudulent and subsequently retracted by the publisher.[15]

Pharmacology[edit]

Curcumin, which shows positive results in most drug discovery assays, is regarded as a false lead that medicinal chemists include among "pan-assay interference compounds" attracting undue experimental attention while failing to advance as viable therapeutic or drug leads.[5][6][16] In vitro, curcumin inhibits certain epigenetic enzymes (the histone deacetylases: HDAC1, HDAC3, HDAC8), transcriptional co-activator proteins (the p300 histone acetyltransferase)[17][18][19] and the arachidonate 5-lipoxygenase enzyme.[20]
In Phase I clinical trials, curcumin had poor bioavailability, was rapidly metabolized, retained low levels in plasma and tissues, and was extensively and rapidly excreted, factors that make its in vivo bioactivity unlikely and difficult to accurately assess.[5][21] Curcumin appears to reduce circulating C-reactive protein in human subjects, although no dose-response relationship was established.[22] Factors that limit the bioactivity of curcumin or its analogs include chemical instability, water insolubility, absence of potent and selective target activity, low bioavailability, limited tissue distribution, extensive metabolism, and potential for toxicity.[5]

Toxicity[edit]

Two preliminary clinical studies in cancer patients consuming high doses of curcumin (up to 8 grams per day for 3–4 months) showed no toxicity, though some subjects reported mild nausea or diarrhea.[23]

Alternative medicine[edit]

Some alternative medicine practitioners give curcumin (as turmeric) intravenously as a treatment for a wide range of health problems, leading to a death in California in 2017[24] despite the absence of reliable clinical research and concerns about safety or efficacy.[5][6]
Posted by at No comments:
Subscribe to: Comments (Atom)