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Hydroxamate
A hydroxamic acid is a class of organic compounds bearing the functional group RC(O)N(OH)R', with R and R' as organic residues and CO as a carbonyl group. They are amides (RC(O)NHR') wherein the NH center has an OH substitution. They are often used as metal chelators. Synthesis and reactions Hydroxamic acids are usually prepared from either esters or acid chlorides by a reaction with hydroxylamine salts. For the synthesis of benzohydroxamic acid, the overall equation is: :C6H5CO2Me + NH2OH → C6H5C(O)NHOH + MeOH Hydroxamic acids can also be synthesized from aldehydes and ''N''-sulfonylhydroxylamine via the Angeli-Rimini reaction. A well-known reaction of hydroxamic acid esters is the Lossen rearrangement. Coordination chemistry and biochemistry File:Ferrichrome.svg, Ferrichrome File:Deferoxamine-2D-skeletal.png , Deferoxamine File:Rhodotorulic acid.svg, Rhodotorulic acid File:Fe(hydroxamate)3.svg, Fe(III) complex of triacetylfusarinine Many hydroxamates have ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Siderophore
Siderophores (Greek: "iron carrier") are small, high-affinity iron- chelating compounds that are secreted by microorganisms such as bacteria and fungi. They help the organism accumulate iron. Although a widening range of siderophore functions is now being appreciated. Siderophores are among the strongest (highest affinity) Fe3+ binding agents known. Phytosiderophores are siderophores produced by plants. Scarcity of soluble iron Despite being one of the most abundant elements in the Earth's crust, iron is not readily bioavailable. In most aerobic environments, such as the soil or sea, iron exists in the ferric (Fe3+) state, which tends to form insoluble rust-like solids. To be effective, nutrients must not only be available, they must be soluble. Microbes release siderophores to scavenge iron from these mineral phases by formation of soluble Fe3+ complexes that can be taken up by active transport mechanisms. Many siderophores are nonribosomal peptides, although several are biosynt ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ferrichrome
Ferrichrome is a cyclic hexa-peptide that forms a complex with iron atoms. It is a siderophore composed of three glycine and three modified ornithine residues with hydroxamate groups N(OH)C(=O)C- The 6 oxygen atoms from the three hydroxamate groups bind Fe(III) in near perfect octahedral coordination. Ferrichrome was first isolated in 1952, and has been found to be produced by fungi of the genera ''Aspergillus'', ''Ustilago'', and ''Penicillium''. However, at the time there was no understanding regarding its involvement and contribution to iron transport. It was not until 1957 because of Joe Neilands work, where he first noted that Ferrichrome was able to act as an iron transport agent. Biological function Ferrichrome is a siderophore, which are metal chelating agents that have a low molecular mass and are produced by microorganisms and plants growing under low iron conditions. The main function of siderophores is to chelate ferric iron (Fe3+) from insoluble minerals from th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hydroxamic Acids
A hydroxamic acid is a class of organic compounds bearing the functional group RC(O)N(OH)R', with R and R' as organic residues and CO as a carbonyl group. They are amides (RC(O)NHR') wherein the NH center has an OH substitution. They are often used as metal chelators. Synthesis and reactions Hydroxamic acids are usually prepared from either esters or acid chlorides by a reaction with hydroxylamine salts. For the synthesis of benzohydroxamic acid, the overall equation is: :C6H5CO2Me + NH2OH → C6H5C(O)NHOH + MeOH Hydroxamic acids can also be synthesized from aldehydes and ''N''-sulfonylhydroxylamine via the Angeli-Rimini reaction. A well-known reaction of hydroxamic acid esters is the Lossen rearrangement. Coordination chemistry and biochemistry File:Ferrichrome.svg, Ferrichrome File:Deferoxamine-2D-skeletal.png , Deferoxamine File:Rhodotorulic acid.svg, Rhodotorulic acid File:Fe(hydroxamate)3.svg, Fe(III) complex of triacetylfusarinine Many hydroxamates have ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HDAC Inhibitor
Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that inhibit histone deacetylases. HDIs have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics. More recently they are being investigated as possible treatments for cancers, parasitic and inflammatory diseases. Cellular biochemistry/pharmacology To carry out gene expression, a cell must control the coiling and uncoiling of DNA around histones. This is accomplished with the assistance of histone acetyl transferases (HAT), which acetylate the lysine residues in core histones leading to a less compact and more transcriptionally active euchromatin, and, on the converse, the actions of histone deacetylases (HDAC), which remove the acetyl groups from the lysine residues leading to the formation of a condensed and transcriptionally silenced chromatin. Reversible modification of the terminal tails of core histones constitutes the major epigenetic mechanism for ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Rhodotorulic Acid
Rhodotorulic acid is the smallest of the 2,5-diketopiperazine family of hydroxamate siderophores which are high-affinity chelating agents for ferric iron, produced by bacterial and fungal phytopathogens for scavenging iron from the environment. It is a tetradentate ligand, meaning it binds one iron atom in four locations (two hydroxamate and two lactam moieties), and forms Fe2(siderophore)3 complexes to fulfill an octahedral coordination for iron. Rhodotorulic acid occurs in basidiomycetous yeasts and was found to retard the spore germination of the fungus ''Botrytis cinerea''. In combination with yeast ''R. glutinis'' it was found to be effective in the biocontrol of iprodione Iprodione is a hydantoin fungicide and nematicide. Application Iprodione is used on crops affected by Botrytis bunch rot, Brown rot, Sclerotinia and other fungal diseases in plants. It is currently applied in a variety of crops: fruit, vegetable ...-resistant ''B. cinerea'' of apple wounds caused by th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a carbonyl group is often referred to as a carbonyl compound. The term carbonyl can also refer to carbon monoxide as a ligand in an inorganic or organometallic complex (a metal carbonyl, e.g. nickel carbonyl). The remainder of this article concerns itself with the organic chemistry definition of carbonyl, where carbon and oxygen share a double bond. Carbonyl compounds In organic chemistry, a carbonyl group characterizes the following types of compounds: Other organic carbonyls are urea and the carbamates, the derivatives of acyl chlorides chloroformates and phosgene, carbonate esters, thioesters, lactones, lactams, hydroxamates, and isocyanates. Examples of inorganic carbonyl compounds are carbon dioxide and carbonyl su ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Trichostatin A
Trichostatin A (TSA) is an organic compound that serves as an antifungal antibiotic and selectively inhibits the class I and II mammalian histone deacetylase (HDAC) families of enzymes, but not class III HDACs (i.e., sirtuins). However, there are recent reports of the interactions of this molecule with Sirt 6 protein. TSA inhibits the eukaryotic cell cycle during the beginning of the growth stage. TSA can be used to alter gene expression by interfering with the removal of acetyl groups from histones (histone deacetylases, HDAC) and therefore altering the ability of DNA transcription factors to access the DNA molecules inside chromatin. It is a member of a larger class of histone deacetylase inhibitors (HDIs or HDACIs) that have a broad spectrum of epigenetic activities. Thus, TSA has some potential as an anti-cancer drug. One suggested mechanism is that TSA promotes the expression of apoptosis-related genes, leading to cancerous cells surviving at lower rates, thus slowing the p ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lossen Rearrangement
The Lossen rearrangement is the conversion of a hydroxamate ester to an isocyanate. Typically O-acyl, sulfonyl, or phosphoryl O-derivative are employed. The isocyanate can be used further to generate ureas in the presence of amines or generate amines in the presence of H2O. Reaction mechanism The mechanism below begins with an O-acylated hydroxamic acid derivative that is treated with base to form an isocyanate that generates an amine and CO2 gas in the presence of H2O. The hydroxamic acid derivative is first converted to its conjugate base by abstraction of a hydrogen by a base. Spontaneous rearrangement releases a carboxylate anion to produce the isocyanate intermediate. The isocyanate is then hydrolyzed in the presence of H2O. Finally, the respective amine and CO2 are generated by abstraction of a proton with a base and decarboxylation. Hydroxamic acids are commonly synthesized from their corresponding esters. Historical references * * * See also * Curtius rearrangem ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DXP Reductoisomerase
DXP reductoisomerase (1-deoxy-D-xylulose 5-phosphate reductoisomerase or DXR) is an enzyme that interconverts 1-deoxy-D-xylulose 5-phosphate (DXP) and 2-C-methyl-D-erythritol 4-phosphate (MEP). Image:DOXP.png, 1-Deoxy-D-xylulose 5-phosphate Image:MEP.png, 2-C-methyl-D-erythritol 4-phosphate It is classified under . It is normally abbreviated DXR, but it is sometimes named IspC, as the product of the ''ispC'' gene. DXR is part of the MEP pathway (nonmevalonate pathway) of isoprenoid precursor biosynthesis. DXR is inhibited by fosmidomycin. This enzyme is required for terpenoid biosynthesis in some organisms, since it is a key enzyme on the MEP pathway for the production of the isoprenoid precursors IPP and DMAPP. In ''Arabidopsis thaliana'' 1-deoxy-D-xylulose 5-phosphate reductoisomerase is the first committed enzyme of the MEP pathway for isoprenoid The terpenoids, also known as isoprenoids, are a class of naturally occurring organic chemicals derived from the 5-ca ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fosmidomycin
Fosmidomycin is an antibiotic that was originally isolated from culture broths of bacteria of the genus '' Streptomyces''. It specifically inhibits DXP reductoisomerase, a key enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. It is a structural analogue of 2-C-methyl-D-erythrose 4-phosphate. It inhibits the '' E. coli'' enzyme with a KI value of 38 nM (4), MTB at 80 nM, and the ''Francisella'' enzyme at 99 nM. Several mutations in the E. coli DXP reductoisomerase were found to confer resistance to fosmidomycin. Use in malaria The discovery of the non-mevalonate pathway in malaria parasites has indicated the use of fosmidomycin and other such inhibitors as antimalarial drugs. Indeed, fosmidomycin has been tested in combination treatment with clindamycin for treatment of malaria with favorable results. It has been shown that an increase in copy number of the target enzyme (DXP reductoisomerase) correlates with ''in vitro'' fosmidomycin resistance in the lethal ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Panobinostat
Panobinostat, sold under the brand name Farydak, is a medication used for the treatment of multiple myeloma. It is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor (pan-HDAC inhibitor).Table 3: Select epigenetic inhibitors in various stages of development from Panobinostat was approved for medical use in the United States in February 2015, and in the European Union in August 2015. However, in March 2022, it was withdrawn in the United States. Medical uses Panobinostat is used in combination with the anti-cancer drug and the cor ...[...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Belinostat
Belinostat (trade name Beleodaq, previously known as PXD101) is a histone deacetylase inhibitor drug developed by TopoTarget for the treatment of hematological malignancies and solid tumors. It was approved in July 2014 by the US FDA to treat peripheral T-cell lymphoma. In 2007 preliminary results were released from the Phase II clinical trial of intravenous belinostat in combination with carboplatin and paclitaxel for relapsed ovarian cancer. Final results in late 2009 of a phase II trial for T-cell lymphoma were encouraging. Belinostat has been granted orphan drug and fast track designation by the FDA, and was approved in the US for the use against peripheral T-cell lymphoma on 3 July 2014. It is not approved in Europe . The approved pharmaceutical formulation is given intravenously. Belinostat is primarily metabolized by UGT1A1; the initial dose should be reduced if the recipient is known to be homozygous for the UGT1A1*28 allele An allele (, ; ; modern formation from G ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
