1.
Jmol
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Jmol is computer software for molecular modelling chemical structures in 3-dimensions. Jmol returns a 3D representation of a molecule that may be used as a teaching tool and it is written in the programming language Java, so it can run on the operating systems Windows, macOS, Linux, and Unix, if Java is installed. It is free and open-source software released under a GNU Lesser General Public License version 2.0, a standalone application and a software development kit exist that can be integrated into other Java applications, such as Bioclipse and Taverna. A popular feature is an applet that can be integrated into web pages to display molecules in a variety of ways, for example, molecules can be displayed as ball-and-stick models, space-filling models, ribbon diagrams, etc. Jmol supports a range of chemical file formats, including Protein Data Bank, Crystallographic Information File, MDL Molfile. There is also a JavaScript-only version, JSmol, that can be used on computers with no Java, the Jmol applet, among other abilities, offers an alternative to the Chime plug-in, which is no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS9. Jmol requires Java installation and operates on a variety of platforms. For example, Jmol is fully functional in Mozilla Firefox, Internet Explorer, Opera, Google Chrome, fast and Scriptable Molecular Graphics in Web Browsers without Java3D
2.
ChEMBL
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ChEMBL or ChEMBLdb is a manually curated chemical database of bioactive molecules with drug-like properties. It is maintained by the European Bioinformatics Institute, of the European Molecular Biology Laboratory, based at the Wellcome Trust Genome Campus, Hinxton, the database, originally known as StARlite, was developed by a biotechnology company called Inpharmatica Ltd. later acquired by Galapagos NV. The data was acquired for EMBL in 2008 with an award from The Wellcome Trust, resulting in the creation of the ChEMBL chemogenomics group at EMBL-EBI, the ChEMBL database contains compound bioactivity data against drug targets. Bioactivity is reported in Ki, Kd, IC50, and EC50, data can be filtered and analyzed to develop compound screening libraries for lead identification during drug discovery. ChEMBL version 2 was launched in January 2010, including 2.4 million bioassay measurements covering 622,824 compounds and this was obtained from curating over 34,000 publications across twelve medicinal chemistry journals. ChEMBLs coverage of available bioactivity data has grown to become the most comprehensive ever seen in a public database, in October 2010 ChEMBL version 8 was launched, with over 2.97 million bioassay measurements covering 636,269 compounds. ChEMBL_10 saw the addition of the PubChem confirmatory assays, in order to integrate data that is comparable to the type, ChEMBLdb can be accessed via a web interface or downloaded by File Transfer Protocol. It is formatted in a manner amenable to computerized data mining, ChEMBL is also integrated into other large-scale chemistry resources, including PubChem and the ChemSpider system of the Royal Society of Chemistry. In addition to the database, the ChEMBL group have developed tools and these include Kinase SARfari, an integrated chemogenomics workbench focussed on kinases. The system incorporates and links sequence, structure, compounds and screening data, the primary purpose of ChEMBL-NTD is to provide a freely accessible and permanent archive and distribution centre for deposited data. July 2012 saw the release of a new data service, sponsored by the Medicines for Malaria Venture. The data in this service includes compounds from the Malaria Box screening set, myChEMBL, the ChEMBL virtual machine, was released in October 2013 to allow users to access a complete and free, easy-to-install cheminformatics infrastructure. In December 2013, the operations of the SureChem patent informatics database were transferred to EMBL-EBI, in a portmanteau, SureChem was renamed SureChEMBL. 2014 saw the introduction of the new resource ADME SARfari - a tool for predicting and comparing cross-species ADME targets
3.
ChemSpider
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ChemSpider is a database of chemicals. ChemSpider is owned by the Royal Society of Chemistry, the database contains information on more than 50 million molecules from over 500 data sources including, Each chemical is given a unique identifier, which forms part of a corresponding URL. This is an approach to develop an online chemistry database. The search can be used to widen or restrict already found results, structure searching on mobile devices can be done using free apps for iOS and for the Android. The ChemSpider database has been used in combination with text mining as the basis of document markup. The result is a system between chemistry documents and information look-up via ChemSpider into over 150 data sources. ChemSpider was acquired by the Royal Society of Chemistry in May,2009, prior to the acquisition by RSC, ChemSpider was controlled by a private corporation, ChemZoo Inc. The system was first launched in March 2007 in a release form. ChemSpider has expanded the generic support of a database to include support of the Wikipedia chemical structure collection via their WiChempedia implementation. A number of services are available online. SyntheticPages is an interactive database of synthetic chemistry procedures operated by the Royal Society of Chemistry. Users submit synthetic procedures which they have conducted themselves for publication on the site and these procedures may be original works, but they are more often based on literature reactions. Citations to the published procedure are made where appropriate. They are checked by an editor before posting. The pages do not undergo formal peer-review like a journal article. The comments are moderated by scientific editors. The intention is to collect practical experience of how to conduct useful chemical synthesis in the lab, while experimental methods published in an ordinary academic journal are listed formally and concisely, the procedures in ChemSpider SyntheticPages are given with more practical detail. Comments by submitters are included as well, other publications with comparable amounts of detail include Organic Syntheses and Inorganic Syntheses
4.
PubChem
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PubChem is a database of chemical molecules and their activities against biological assays. The system is maintained by the National Center for Biotechnology Information, a component of the National Library of Medicine, PubChem can be accessed for free through a web user interface. Millions of compound structures and descriptive datasets can be downloaded via FTP. PubChem contains substance descriptions and small molecules with fewer than 1000 atoms and 1000 bonds, more than 80 database vendors contribute to the growing PubChem database. PubChem consists of three dynamically growing primary databases, as of 28 January 2016, Compounds,82.6 million entries, contains pure and characterized chemical compounds. Substances,198 million entries, contains also mixtures, extracts, complexes, bioAssay, bioactivity results from 1.1 million high-throughput screening programs with several million values. PubChem contains its own online molecule editor with SMILES/SMARTS and InChI support that allows the import and export of all common chemical file formats to search for structures and fragments. In the text search form the database fields can be searched by adding the name in square brackets to the search term. A numeric range is represented by two separated by a colon. The search terms and field names are case-insensitive, parentheses and the logical operators AND, OR, and NOT can be used. AND is assumed if no operator is used, example,0,5000,50,10 -5,5 PubChem was released in 2004. The American Chemical Society has raised concerns about the publicly supported PubChem database and they have a strong interest in the issue since the Chemical Abstracts Service generates a large percentage of the societys revenue. To advocate their position against the PubChem database, ACS has actively lobbied the US Congress, soon after PubChems creation, the American Chemical Society lobbied U. S. Congress to restrict the operation of PubChem, which they asserted competes with their Chemical Abstracts Service
5.
International Chemical Identifier
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Initially developed by IUPAC and NIST from 2000 to 2005, the format and algorithms are non-proprietary. The continuing development of the standard has supported since 2010 by the not-for-profit InChI Trust. The current version is 1.04 and was released in September 2011, prior to 1.04, the software was freely available under the open source LGPL license, but it now uses a custom license called IUPAC-InChI Trust License. Not all layers have to be provided, for instance, the layer can be omitted if that type of information is not relevant to the particular application. InChIs can thus be seen as akin to a general and extremely formalized version of IUPAC names and they can express more information than the simpler SMILES notation and differ in that every structure has a unique InChI string, which is important in database applications. Information about the 3-dimensional coordinates of atoms is not represented in InChI, the InChI algorithm converts input structural information into a unique InChI identifier in a three-step process, normalization, canonicalization, and serialization. The InChIKey, sometimes referred to as a hashed InChI, is a fixed length condensed digital representation of the InChI that is not human-understandable. The InChIKey specification was released in September 2007 in order to facilitate web searches for chemical compounds and it should be noted that, unlike the InChI, the InChIKey is not unique, though collisions can be calculated to be very rare, they happen. In January 2009 the final 1.02 version of the InChI software was released and this provided a means to generate so called standard InChI, which does not allow for user selectable options in dealing with the stereochemistry and tautomeric layers of the InChI string. The standard InChIKey is then the hashed version of the standard InChI string, the standard InChI will simplify comparison of InChI strings and keys generated by different groups, and subsequently accessed via diverse sources such as databases and web resources. Every InChI starts with the string InChI= followed by the version number and this is followed by the letter S for standard InChIs. The remaining information is structured as a sequence of layers and sub-layers, the layers and sub-layers are separated by the delimiter / and start with a characteristic prefix letter. The six layers with important sublayers are, Main layer Chemical formula and this is the only sublayer that must occur in every InChI. The atoms in the formula are numbered in sequence, this sublayer describes which atoms are connected by bonds to which other ones. Describes how many hydrogen atoms are connected to each of the other atoms, the condensed,27 character standard InChIKey is a hashed version of the full standard InChI, designed to allow for easy web searches of chemical compounds. Most chemical structures on the Web up to 2007 have been represented as GIF files, the full InChI turned out to be too lengthy for easy searching, and therefore the InChIKey was developed. With all databases currently having below 50 million structures, such duplication appears unlikely at present, a recent study more extensively studies the collision rate finding that the experimental collision rate is in agreement with the theoretical expectations. Example, Morphine has the structure shown on the right, as the InChI cannot be reconstructed from the InChIKey, an InChIKey always needs to be linked to the original InChI to get back to the original structure
6.
Simplified molecular-input line-entry system
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The simplified molecular-input line-entry system is a specification in form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules, the original SMILES specification was initiated in the 1980s. It has since modified and extended. In 2007, a standard called OpenSMILES was developed in the open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. The Environmental Protection Agency funded the project to develop SMILES. It has since modified and extended by others, most notably by Daylight Chemical Information Systems. In 2007, a standard called OpenSMILES was developed by the Blue Obelisk open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, in July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is generally considered to have the advantage of being slightly more human-readable than InChI, the term SMILES refers to a line notation for encoding molecular structures and specific instances should strictly be called SMILES strings. However, the term SMILES is also used to refer to both a single SMILES string and a number of SMILES strings, the exact meaning is usually apparent from the context. The terms canonical and isomeric can lead to confusion when applied to SMILES. The terms describe different attributes of SMILES strings and are not mutually exclusive, typically, a number of equally valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol, algorithms have been developed to generate the same SMILES string for a given molecule, of the many possible strings, these algorithms choose only one of them. This SMILES is unique for each structure, although dependent on the algorithm used to generate it. These algorithms first convert the SMILES to a representation of the molecular structure. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database, there is currently no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, and these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES
7.
Chemical formula
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These are limited to a single typographic line of symbols, which may include subscripts and superscripts. A chemical formula is not a name, and it contains no words. Although a chemical formula may imply certain simple chemical structures, it is not the same as a full chemical structural formula. Chemical formulas can fully specify the structure of only the simplest of molecules and chemical substances, the simplest types of chemical formulas are called empirical formulas, which use letters and numbers indicating the numerical proportions of atoms of each type. Molecular formulas indicate the numbers of each type of atom in a molecule. For example, the formula for glucose is CH2O, while its molecular formula is C6H12O6. This is possible if the relevant bonding is easy to show in one dimension, an example is the condensed molecular/chemical formula for ethanol, which is CH3-CH2-OH or CH3CH2OH. For reasons of structural complexity, there is no condensed chemical formula that specifies glucose, chemical formulas may be used in chemical equations to describe chemical reactions and other chemical transformations, such as the dissolving of ionic compounds into solution. A chemical formula identifies each constituent element by its chemical symbol, in empirical formulas, these proportions begin with a key element and then assign numbers of atoms of the other elements in the compound, as ratios to the key element. For molecular compounds, these numbers can all be expressed as whole numbers. For example, the formula of ethanol may be written C2H6O because the molecules of ethanol all contain two carbon atoms, six hydrogen atoms, and one oxygen atom. Some types of compounds, however, cannot be written with entirely whole-number empirical formulas. An example is boron carbide, whose formula of CBn is a variable non-whole number ratio with n ranging from over 4 to more than 6.5. When the chemical compound of the consists of simple molecules. These types of formulas are known as molecular formulas and condensed formulas. A molecular formula enumerates the number of atoms to reflect those in the molecule, so that the formula for glucose is C6H12O6 rather than the glucose empirical formula. However, except for very simple substances, molecular chemical formulas lack needed structural information, for simple molecules, a condensed formula is a type of chemical formula that may fully imply a correct structural formula. For example, ethanol may be represented by the chemical formula CH3CH2OH
8.
Phenol
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Phenol, also known as carbolic acid, is an aromatic organic compound with the molecular formula C6H5OH. It is a crystalline solid that is volatile. The molecule consists of a phenyl group bonded to a hydroxyl group and it is mildly acidic and requires careful handling due to its propensity to cause chemical burns. Phenol was first extracted from tar, but today is produced on a large scale from petroleum. It is an important industrial commodity as a precursor to many materials and it is primarily used to synthesize plastics and related materials. Phenol and its derivatives are essential for production of polycarbonates, epoxies, Bakelite, nylon, detergents, herbicides such as phenoxy herbicides. Phenol is appreciably soluble in water, with about 84.2 g dissolving in 1000 mL, homogeneous mixtures of phenol and water at phenol to water mass ratios of ~2.6 and higher are possible. The sodium salt of phenol, sodium phenoxide, is far more water-soluble and it reacts completely with aqueous NaOH to lose H+, whereas most alcohols react only partially. One explanation for the increased acidity over alcohols is resonance stabilization of the anion by the aromatic ring. In this way, the charge on oxygen is delocalized on to the ortho. In another explanation, increased acidity is the result of orbital overlap between the lone pairs and the aromatic system. The pKa of the enol of acetone is 10.9, the acidities of phenol and acetone enol diverge in the gas phase owing to the effects of solvation. About 1⁄3 of the acidity of phenol is attributable to inductive effects. Phenolate esters are more stable toward hydrolysis than acid anhydrides and acyl halides but are sufficiently reactive under mild conditions to facilitate the formation of amide bonds, Phenol exhibits keto-enol tautomerism with its unstable keto tautomer cyclohexadienone, but only a tiny fraction of phenol exists as the keto form. The equilibrium constant for enolisation is approximately 10−13, meaning only one in every ten trillion molecules is in the keto form at any moment. The small amount of stabilisation gained by exchanging a C=C bond for a C=O bond is more than offset by the large destabilisation resulting from the loss of aromaticity, Phenol therefore exists essentially entirely in the enol form. Phenoxides are enolates stabilised by aromaticity, under normal circumstances, phenoxide is more reactive at the oxygen position, but the oxygen position is a hard nucleophile whereas the alpha-carbon positions tend to be soft. Phenol is highly reactive toward electrophilic aromatic substitution as the oxygen atoms pi electrons donate electron density into the ring, by this general approach, many groups can be appended to the ring, via halogenation, acylation, sulfonation, and other processes
9.
Cistus salviifolius
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Cistus salviifolius, common names sage-leaved rock-rose, salvia cistus or Gallipoli rose, is a perennial ligneous plant of the family Cistaceae. The genus name Cistus derives from the Ancient Greek words κίσϑος meaning basket, Cistus salviifolius has spreading stems covered by clumpy hairs. This bushy shrub reaches on average 30–60 centimetres in height, with a maximum of 100 centimetres, the oval-shaped green leaves are 1 to 4 centimeters long, opposite, reticulate, tomentose on both sides, with a short petiole. The inflorescence holds one or more flowers, long-stalked, arranged at the leaf axils. The five white petals have a spot at the base. The stamens are yellow and the anthers shed abundant yellow pollen. This plant is pollinated by insects entomophily, especially bees, the flowering period extends from April through May. The fruit is a capsule, 5–7 mm long. Cistus salviifolius cultivated in the industry, and grown in gardens and public landscapes, often for its drought-tolerant. This showy wildflower is native to the Mediterranean region, in southern Europe and parts of Western Asia and this plant prefers dry hills, scrubs and open woodlands, at an altitude of 0–1,200 metres above sea level. It grows very quickly after a fire and it also contains ellagitannins of the punicalagin type. Jepson Manual Treatment - Cistus salviifolius
10.
In vitro
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In vitro studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. In contrast, in studies are those conducted in animals, including humans. In vitro studies are conducted using components of an organism that have been isolated from their biological surroundings, such as microorganisms, cells. For example, microrganisms or cells can be studied in artificial culture media, colloquially called test-tube experiments, these studies in biology, medicine, and their subdisciplines are traditionally done in test tubes, flasks, Petri dishes, etc. They now involve the range of techniques used in molecular biology. In contrast, studies conducted in living beings are called in vivo, polymerase chain reaction is a method for selective replication of specific DNA and RNA sequences in the test tube. Protein purification involves the isolation of a protein of interest from a complex mixture of proteins. In vitro fertilization is used to allow spermatozoa to fertilize eggs in a culture dish before implanting the resulting embryo or embryos into the uterus of the prospective mother and these ADME process parameters can then be integrated into so called physiologically based pharmacokinetic models or PBPK. In vitro studies permit a species-specific, simpler, more convenient, just as studies in whole animals more and more replace human trials, so are in vitro studies replacing studies in whole animals. This complexity makes it difficult to identify the interactions between individual components and to explore their basic biological functions, in vitro work simplifies the system under study, so the investigator can focus on a small number of components. Another advantage of in vitro methods is that cells can be studied without extrapolation from an experimental animals cellular response. Investigators doing in vitro work must be careful to avoid over-interpretation of their results, for example, scientists developing a new viral drug to treat an infection with a pathogenic virus may find that a candidate drug functions to prevent viral replication in an in vitro setting. However, before this drug is used in the clinic, it must progress through a series of in vivo trials to determine if it is safe and effective in intact organisms. Results obtained from in vitro experiments cannot usually be transposed, as is, building a consistent and reliable extrapolation procedure from in vitro results to in vivo is therefore extremely important. However, increasingly sophisticated in vitro experiments collect increasingly numerous, complex, mathematical models, such as systems biology models, are much needed here. In pharmacology, IVIVE can be used to approximate pharmacokinetics or pharmacodynamics and that indicates that extrapolating effects observed in vitro needs a quantitative model of in vivo PK. Physiologically based PK models are generally accepted to be central to the extrapolations, in these conditions, developing a simple PD model of the dose–response relationship observed in vitro, and transposing it without changes to predict in vivo effects is not enough
11.
Analgesic
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An analgesic or painkiller is any member of the group of drugs used to achieve analgesia, relief from pain. Analgesic drugs act in various ways on the peripheral and central nervous systems and they are distinct from anesthetics, which temporarily affect, and in some instances completely eliminate, sensation. Analgesics include paracetamol, the nonsteroidal anti-inflammatory drugs such as the salicylates, when choosing analgesics, the severity and response to other medication determines the choice of agent, the World Health Organization pain ladder specifies mild analgesics as its first step. Topical nonsteroidal anti-inflammatory drugs provided pain relief in common such as muscle sprains. Since the side effects are also lesser, topical preparations could be preferred over oral medications in these conditions, each different type of analgesic has its own associated side effects. Drugs for pain are typically classified by chemical structure and they may also be classified in other ways. Sometimes they are classified by use for classes of medical condition. Other times they are sorted by the needs of populations who would use them. They might be listed by availability in an area, perhaps to prevent recommending a drug which is illegal in one place even if it is easily available elsewhere. Paracetamol, also known as acetaminophen or APAP, is a used to treat pain. It is typically used for mild to moderate pain, in combination with opioid pain medication, paracetamol is used for more severe pain such as cancer pain and after surgery. It is typically used either by mouth or rectally but is also available intravenously, effects last between two and four hours. Paracetamol is classified as a mild analgesic, paracetamol is generally safe at recommended doses. Nonsteroidal anti-inflammatory drugs, are a class that groups together drugs that provide analgesic and antipyretic effects. The most prominent members of group of drugs, aspirin. These drugs have been derived from NSAIDs, the cyclooxygenase enzyme inhibited by NSAIDs was discovered to have at least 2 different versions, COX1 and COX2. Research suggested most of the effects of NSAIDs to be mediated by blocking the COX1 enzyme. Thus, the COX2 inhibitors were developed to inhibit only the COX2 enzyme and these drugs are equally effective analgesics when compared with NSAIDs, but cause less gastrointestinal hemorrhage in particular
12.
PubMed Identifier
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PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine at the National Institutes of Health maintains the database as part of the Entrez system of information retrieval, from 1971 to 1997, MEDLINE online access to the MEDLARS Online computerized database primarily had been through institutional facilities, such as university libraries. PubMed, first released in January 1996, ushered in the era of private, free, home-, the PubMed system was offered free to the public in June 1997, when MEDLINE searches via the Web were demonstrated, in a ceremony, by Vice President Al Gore. Information about the journals indexed in MEDLINE, and available through PubMed, is found in the NLM Catalog. As of 5 January 2017, PubMed has more than 26.8 million records going back to 1966, selectively to the year 1865, and very selectively to 1809, about 500,000 new records are added each year. As of the date,13.1 million of PubMeds records are listed with their abstracts. In 2016, NLM changed the system so that publishers will be able to directly correct typos. Simple searches on PubMed can be carried out by entering key aspects of a subject into PubMeds search window, when a journal article is indexed, numerous article parameters are extracted and stored as structured information. Such parameters are, Article Type, Secondary identifiers, Language, publication type parameter enables many special features. As these clinical girish can generate small sets of robust studies with considerable precision, since July 2005, the MEDLINE article indexing process extracts important identifiers from the article abstract and puts those in a field called Secondary Identifier. The secondary identifier field is to store numbers to various databases of molecular sequence data, gene expression or chemical compounds. For clinical trials, PubMed extracts trial IDs for the two largest trial registries, ClinicalTrials. gov and the International Standard Randomized Controlled Trial Number Register, a reference which is judged particularly relevant can be marked and related articles can be identified. If relevant, several studies can be selected and related articles to all of them can be generated using the Find related data option, the related articles are then listed in order of relatedness. To create these lists of related articles, PubMed compares words from the title and abstract of each citation, as well as the MeSH headings assigned, using a powerful word-weighted algorithm. The related articles function has been judged to be so precise that some researchers suggest it can be used instead of a full search, a strong feature of PubMed is its ability to automatically link to MeSH terms and subheadings. Examples would be, bad breath links to halitosis, heart attack to myocardial infarction, where appropriate, these MeSH terms are automatically expanded, that is, include more specific terms. Terms like nursing are automatically linked to Nursing or Nursing and this important feature makes PubMed searches automatically more sensitive and avoids false-negative hits by compensating for the diversity of medical terminology. The My NCBI area can be accessed from any computer with web-access, an earlier version of My NCBI was called PubMed Cubby
13.
Phenylpropanoid
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The phenylpropanoids are a diverse family of organic compounds that are synthesized by plants from the amino acids phenylalanine and tyrosine. Concentrations of phenylpropanoids within plants are also altered by changes in resource availability, phenylpropanoids and other phenolics are part of the chemical composition of sporopollenin. This substance found in pollen is not exactly known, due to its chemical stability and resistance to degradation by enzymes. Analyses have revealed a mixture of biopolymers, containing mainly long chain fatty acids, phenylpropanoids, phenolics, tracer experiments have shown that phenylalanine is a major precursor, but other carbon sources also contribute. It is likely that sporopollenin is derived from several precursors that are chemically cross-linked to form a rigid structure, phenylalanine is first converted to cinnamic acid by the action of the enzyme phenylalanine ammonia-lyase. Some plants, mainly monocotyledonous, use tyrosine to synthesize p-coumaric acid by the action of the bifunctional enzyme Phenylalanine/tyrosine ammonia-lyase, a series of enzymatic hydroxylations and methylations leads to coumaric acid, caffeic acid, ferulic acid, 5-hydroxyferulic acid, and sinapic acid. Conversion of these acids to their corresponding esters produces some of the components of herb and flower fragrances. Ethyl cinnamate is a common example, reduction of the carboxylic acid functional groups in the cinnamic acids provides the corresponding aldehydes, such as cinnamaldehyde. Further reduction provides monolignols including coumaryl alcohol, coniferyl alcohol, and sinapyl alcohol, the monolignols are monomers that are polymerized to generate various forms of lignin and suberin, which are used as a structural component of plant cell walls. The phenylpropenes, including eugenol, chavicol, safrole and estragole, are derived from the monolignols. These compounds are the constituents of various essential oils. Hydroxylation of cinnamic acid in the 4-position by trans-cinnamate 4-monooxygenase leads to p-coumaric acid, another use of p-coumaric acid via its thioester with coenzyme A, i. e. 4-coumaroyl-CoA, is the production of chalcones. This is achieved with the addition of 3 malonyl-CoA molecules and their cyclization into a phenyl group. Chalcones are the precursors of all flavonoids, a class of phytochemicals. Stilbenoids, such as resveratrol, are hydroxylated derivatives of stilbene and they are formed through an alternative cyclization of cinnamoyl-CoA or 4-coumaroyl-CoA. In the orchid Phalaenopsis, phenylpropanoid enzymes are enhanced in the process of plant acclimatisation at different levels of photosynthetic photon flux, Physiology and Molecular Biology of Phenylpropanoid Metabolism. Annual Review of Plant Physiology and Plant Molecular Biology
14.
Chromone
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Chromone is a derivative of benzopyran with a substituted keto group on the pyran ring. It is an isomer of coumarin, derivatives of chromone are collectively known as chromones. Most, though not all, chromones are also phenylpropanoids,6, 7-dimethoxy-2, 3-dihydrochromone has been isolated from Sarcolobus globosus. Eucryphin, a chromone rhamnoside, can be isolated from the bark of Eucryphia cordifolia, cromolyn was found to inhibit antigen challenge as well as stress induced symptoms. Cromoglicate is used as a mast cell stabilizer in allergic rhinitis, asthma, nedocromil sodium was found to have a somewhat longer half-life than cromolyn, however, production was discontinued in the US in 2008. Furanochromones Coumarin - a structural isomer CID from PubChem - 4-chromone Chromones at the US National Library of Medicine Medical Subject Headings Synthesis at organic-chemistry. org
15.
Cinnamaldehyde
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Cinnamaldehyde is an organic compound with the formula C6H5CH=CHCHO. Occurring naturally as predominately the trans isomer, it gives cinnamon its flavor and odor and it is a flavonoid that is naturally synthesized by the shikimate pathway. This pale yellow, viscous liquid occurs in the bark of cinnamon trees, the essential oil of cinnamon bark is about 50% cinnamaldehyde. Cinnamaldehyde was isolated from cinnamon essential oil in 1834 by Dumas and Péligot, the molecule consists of a benzene ring attached to an unsaturated aldehyde. As such, the molecule can be viewed as a derivative of acrolein and its color is due to the π → π* transition, increased conjugation in comparison with acrolein shifts this band towards the visible. The biosynthesis of cinnamaldehyde begins with deamination of L-phenylalalanine into cinnamic acid by the action of phenylalanine ammonia lyase, PAL catalyzes this reaction by a non-oxidative deamination. This deamination relies on the MIO prosthetic group of PAL, PAL gives rise to trans-cinnamic acid. In the second step, 4-coumarate, CoA ligase converts cinnamic acid to cinnamoyl-CoA by an acid-thiol ligation, 4CL uses ATP to catalyze the formation of cinnamoyl-CoA. 4CL effects this reaction in two steps, 4CL forms a hydroxycinnamate-AMP anhydride, followed by a nucleophile attack on the carbonyl of the acyl adenylate. Cinnamoyl-CoA is reduced by NADPH catalyzed by CCR to form cinnamaldehyde, several methods of laboratory synthesis exist, but cinnamaldehyde is most economically obtained from the steam distillation of the oil of cinnamon bark. The compound can be prepared from related compounds such as cinnamyl alcohol, cinnamaldehyde occurs widely, and closely related compounds give rise to lignin. All such compounds are biosynthesized starting from phenylalanine, which undergoes conversion, cinnamoyl-CoA reductase is an enzyme responsible for the production of cinnamoyl-CoA from cinnamaldehyde. The most obvious application for cinnamaldehyde is as flavoring in chewing gum, ice cream, candy and it is also used in some perfumes of natural, sweet, or fruity scents. Almond, apricot, butterscotch, and other aromas may partially employ the compound for their pleasant smells, cinnamaldehyde can be used as a food adulterant, powdered beechnut husk aromatized with cinnamaldehyde can be marketed as powdered cinnamon. Some breakfast cereals contain as much as 187 ppm cinnamaldehyde, cinnamaldehyde is also used as a fungicide. Proven effective on over 40 different crops, cinnamaldehyde is typically applied to the systems of plants. Its low toxicity and well-known properties make it ideal for agriculture, cinnamaldehyde is an effective insecticide, and its scent is also known to repel animals, such as cats and dogs. It has been tested as a safe and effective insecticide against mosquito larvae, a concentration of 29 ppm of cinnamaldehyde kills half of Aedes aegypti mosquito larvae in 24 hours
16.
Monolignol
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Monolignols are phytochemicals acting as source materials for biosynthesis of both lignans and lignin. The starting material for production of monolignols is the amino acid phenylalanine, the first reactions in the biosynthesis are shared with the phenylpropanoid pathway, and monolignols are considered to be a part of this group of compounds. There are three main monolignols, coniferyl alcohol, sinapyl alcohol and paracoumaryl alcohol, for example, Norway spruce lignin is almost entirely coniferyl alcohol while paracoumaryl alcohol is found almost exclusively in grasses. Monolignols are synthetised in the cytosol as glucosides, the glucose is added to the monolignol to make them water-soluble and to reduce their toxicity. The glucosides are transported through the membrane to the apoplast. The glucose is removed and the monolignols are polymerised into lignin. The phenylpropenes are derived from the monolignols
17.
Coumarin
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Coumarin is a fragrant organic chemical compound in the benzopyrone chemical class, which is a colorless crystalline substance in its standard state. It is a substance found in many plants. The name comes from a French term for the bean, coumarou. It has an odor, readily recognised as the scent of newly-mown hay. Sweet woodruff, meadowsweet, sweet grass and sweet-clover in particular are named for their sweet smell, Coumarin is used in certain perfumes and fabric conditioners. Coumarin was first synthesized in 1868, 4-hydroxycoumarins are a type of vitamin K antagonist. Pharmaceutical coumarins were all developed from the study of sweet clover disease, however, unmodified coumarin itself, as it occurs in plants, has no effect on the vitamin K coagulation system, or on the action of warfarin-type drugs. Coumarin has clinical medical value by itself, as an edema modifier, other biological activities that may lead to other medical uses have been suggested, with varying degrees of evidence. Coumarin is also used as a medium in some dye lasers. The word tonka for tonka beans is taken from the Galibi tongue spoken by natives of French Guiana, it appears in Old Tupi, another language of the same region. The old genus name, Coumarouna, was formed from another Tupi name for tree, the French word for the tonka bean, coumarou, is from this name. Coumarin, named for coumarou was first isolated from Tonka beans and sweet clover in 1820 by A. Vogel of Munich, also in 1820, Nicholas Jean Baptiste Gaston Guibourt of France independently isolated coumarin, but he realized that it was not benzoic acid. In a subsequent essay he presented to the section of the Académie Royale de Médecine. In 1835, the French pharmacist A. Guillemette proved that Vogel, Coumarin was first synthesized in 1868 by the English chemist William Henry Perkin. Coumarin can be prepared by a number of reactions with the Perkin reaction between salicylaldehyde and acetic anhydride being a popular example. The Pechmann condensation provides another route to coumarin and its derivatives, Coumarin is also found in extracts of Justicia pectoralis. Related compounds are found in some but not all specimens of licorice, the biosynthesis of coumarin in plants is via hydroxylation, glycolysis, and cyclization of cinnamic acid. The enzyme encoded by the gene UGT1A8 has glucuronidase activity with many substrates including coumarins, Coumarin has appetite-suppressing properties, which may discourage animals from eating plants which contain it
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Chalcone
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Chalcone is an aromatic ketone and an enone that forms the central core for a variety of important biological compounds, which are known collectively as chalcones or chalconoids. Benzylideneacetophenone is the parent member of the chalcone series, the alternative name given to chalcone are phenyl styryl ketone, benzalacetophenone, β-phenylacrylophenone, ɣ-oxo-α, ɣ-diphenyl-α-propylene and α-phenyl-β-benzoylethylene. Chalcones have two absorption maxima at 280 nm and 340 nm, chalcones can be prepared by an aldol condensation between benzaldehyde and acetophenone in the presence of sodium hydroxide as a catalyst. This reaction has found to work without any solvent at all - a solid-state reaction. The reaction between substituted benzaldehydes and acetophenones can be used as an example of green chemistry in undergraduate education, in a study investigating green syntheses, chalcones were synthesized from the same starting materials in high-temperature water. Substituted chalcones were also synthesised by piperidine-mediated condensation to avoid side reactions such as multiple condensations, polymerizations, an example is the conjugate reduction of the enone by tributyltin hydride, Juliá–Colonna epoxidation Chalcone on reference. md
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Flavonoid
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Flavonoids are a class of plant and fungus secondary metabolites. Chemically, flavonoids have the structure of a 15-carbon skeleton. This carbon structure can be abbreviated C6-C3-C6 and this class was the first to be termed bioflavonoids. The terms flavonoid and bioflavonoid have also more loosely used to describe non-ketone polyhydroxy polyphenol compounds which are more specifically termed flavanoids. The three cycle or heterocycles in the backbone are generally called ring A, B and C. Ring A usually shows a phloroglucinol substitution pattern, Flavonoids are widely distributed in plants, fulfilling many functions. Flavonoids are the most important plant pigments for coloration, producing yellow or red/blue pigmentation in petals designed to attract pollinator animals. In higher plants, flavonoids are involved in UV filtration, symbiotic nitrogen fixation and they may also act as chemical messengers, physiological regulators, and cell cycle inhibitors. Flavonoids secreted by the root of their host plant help Rhizobia in the stage of their symbiotic relationship with legumes like peas, beans, clover. In addition, some flavonoids have inhibitory activity against organisms that cause plant diseases, over 5000 naturally occurring flavonoids have been characterized from various plants. Flavonols, the original such as quercetin, are also found ubiquitously. Further information on sources of flavonoids can be obtained from the US Department of Agriculture flavonoid database. Parsley, both fresh and dried, contains flavones, blueberries are a dietary source of anthocyanidins. Black tea is a source of dietary flavan-3-ols. The citrus flavonoids include hesperidin, quercitrin, rutin, and the flavone tangeritin, Flavonoids exist naturally in cocoa, but because they can be bitter, they are often removed from chocolate, even dark chocolate. Although flavonoids are present in milk chocolate, milk may interfere with their absorption, peanut skin contains significant polyphenol content, including flavonoids. Food composition data for flavonoids were provided by the USDA database on flavonoids, in the United States NHANES survey, mean flavonoid intake was 190 mg/d in adults, with flavan-3-ols as the main contributor. In the European Union, based on data from EFSA, mean flavonoid intake was 140 mg/d, the main type of flavonoids consumed in the EU and USA were flavan-3-ols, mainly from tea, while intake of other flavonoids was considerably lower
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Phenylpropene
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Phenylpropenes, propenylphenols, alkenylbenzenes or allylbenzenes are a class of phenylpropanoids in which a benzene ring has an allyl group attached to it. Phenylpropenes have been used as a precursors for a variety of effective insecticides, dosage determines concern, There is long standing and wide use as flavors at doses low enough to be insignificant, but high doses as in medicinal use can be a concern. Phenylpropene compounds are metabolized to reactive carcinogens which are also rapidly metabolized to safe compounds that are excreted. Thus the metabolism of these molecules quickly progresses from flavor to toxin to safe excretion, alkenylbenzenes at high dose can be activated metabolically to reactive intermediates that bind DNA, but are also rapidly converted to less toxic dihydrodiol or glutathione conjugates. The phenylpropenes, including eugenol, chavicol, safrole and estragole, are derived from the monolignols and these compounds are the primary constituents of various essential oils. Substituted methylenedioxyphenethylamines Apiol Asarone Dillapiole Elemicin Eugenol Methyl eugenol Myristicin
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Stilbenoid
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Stilbenoids are hydroxylated derivatives of stilbene. In biochemical terms, they belong to the family of phenylpropanoids, stilbenoids can be produced by plants and bacteria. Stilbenoids are hydroxylated derivatives of stilbene and have a C6-C2-C6 structure and they belong to the family of phenylpropanoids and share most of their biosynthesis pathway with chalcones. Under UV irradiation, stilbene and its derivatives undergo intramolecular cyclization, oligomeric forms are known as oligostilbenoids. Another example is resveratrol, an antifungal which is found in grapes, Ampelopsin A and Ampelopsin B are resveratrol dimers produced in porcelain berry. A bacterial stilbenoid, -,3, 5-Dihydroxy-4-isopropyl-trans-stilbene, is produced by Photorhabdus which is a symbiont of insect nematodes called Heterorhabditis. Phytoalexins have been suggested by studies to be responsible for resistance to some tree diseases. Chemical Defense Responses of Wilt-Resistant Pine Species, Pinus strobus and P. taeda, against Bursaphelenchus xylophilus Infection
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Lignan
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The lignans are a large group of chemical compounds found in plants. Some examples of lignans are pinoresinol, podophyllotoxin, and steganacin, plant lignans are polyphenolic substances derived from phenylalanine via dimerization of substituted cinnamic alcohols, known as monolignols, to a dibenzylbutane skeleton 2. This reaction is catalysed by enzymes and is often controlled by dirigent proteins. Many natural products, known as phenylpropanoids, are built up of C6C3 units derived from cinnamyl units just as terpene chemistry builds on isoprene units. Structure 3 is a neolignan, a formed by joining the two propylbenzene residues at other than the β-carbon atom of the propyl side chain. When a part of the diet, some plant lignans are metabolized by intestinal bacteria to mammalian lignans enterodiol. Lignans that can be metabolized to mammalian lignans are pinoresinol, lariciresinol, secoisolariciresinol, matairesinol, hydroxymatairesinol, syringaresinol, lignans are one of the major classes of phytoestrogens, which are estrogen-like chemicals and also act as antioxidants. The other classes of phytoestrogens are isoflavones and coumestans, plant lignans are co-passengers of dietary fiber, and therefore fiber-rich food items are often good sources of lignans. Flax seed and sesame seed contain higher levels of lignans than most other foods, the principal lignan precursor found in flaxseed is secoisolariciresinol diglucoside. Other sources of lignans include cereals, soybeans, cruciferous vegetables such as broccoli and cabbage, secoisolariciresinol and matairesinol were the first plant lignans identified in foods. Pinoresinol and lariciresinol are more recently identified plant lignans that contribute substantially to the total dietary lignan intakes, typically, lariciresinol and pinoresinol contribute about 75% to the total lignan intake whereas secoisolariciresinol and matairesinol contribute only about 25%. This distribution may change as the contributions of syringaresinol and hydroxymatairesinol have not properly been quantified in foods, sources of lignans, A recent study shows the complexity of mammalian lignan precursors in the diet. In the table below are a few examples of the 22 analyzed species, lignans serve an antioxidant role in the plants defenses against biotic and abiotic factors, and have shown anti-inflammatory and antioxidant activity in basic research models of human diseases. Lignans may also have anticarcinogenic activities, IUPAC lignan nomenclature Lignan content in food
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Lignin
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Lignin is a class of complex organic polymers that form important structural materials in the support tissues of vascular plants and some algae. Lignins are particularly important in the formation of walls, especially in wood and bark, because they lend rigidity. Chemically, lignins are cross-linked phenolic polymers and he named the substance “lignine”, which is derived from the Latin word lignum, meaning wood. It is one of the most abundant organic polymers on Earth, lignin constitutes 30% of non-fossil organic carbon and 20-35% of the dry mass of wood. The Carboniferous Period is in part defined by the evolution of lignin, the composition of lignin varies from species to species. An example of composition from a sample is 63. 4% carbon,5. 9% hydrogen,0. 7% ash. As a biopolymer, lignin is unusual because of its heterogeneity and its most commonly noted function is the support through strengthening of wood in vascular plants. Global commercial production of lignin is around 1.1 million metric tons per year and is used in a range of low volume, niche applications where the form. Lignin fills the spaces in the wall between cellulose, hemicellulose, and pectin components, especially in vascular and support tissues, xylem tracheids, vessel elements. It is covalently linked to hemicellulose and therefore cross-links different plant polysaccharides, conferring mechanical strength to the cell wall and it is particularly abundant in compression wood but scarce in tension wood, which are types of reaction wood. Lignin plays a part in conducting water in plant stems. The polysaccharide components of plant cell walls are highly hydrophilic and thus permeable to water, the crosslinking of polysaccharides by lignin is an obstacle for water absorption to the cell wall. Thus, lignin makes it possible for the vascular tissue to conduct water efficiently. Lignin is present in all plants, but not in bryophytes. However, it is present in red algae, which seems to suggest that the ancestor of plants. This would suggest that its function was structural, it plays this role in the red alga Calliarthron. Another possibility is that the lignins in red algae and in plants are result of convergent evolution, lignin plays a significant role in the carbon cycle, sequestering atmospheric carbon into the living tissues of woody perennial vegetation. Lignin is one of the most slowly decomposing components of dead vegetation, the resulting soil humus, in general, holds nutrients onto its surface, and hence increases its cation exchange capacity and moisture retention, hence it increases the productivity of soil
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Phenols
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In organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of a hydroxyl group bonded directly to an aromatic hydrocarbon group. The simplest of the class is phenol, which is also called carbolic acid C 6H 5OH, phenolic compounds are classified as simple phenols or polyphenols based on the number of phenol units in the molecule. Synonyms are arenols or aryl alcohols, phenolic compounds are synthesized industrially, they also are produced by plants and microorganisms, with variation between and within species. Although similar to alcohols, phenols have unique properties and are not classified as alcohols and they have higher acidities due to the aromatic rings tight coupling with the oxygen and a relatively loose bond between the oxygen and hydrogen. The acidity of the group in phenols is commonly intermediate between that of aliphatic alcohols and carboxylic acids. Phenols can have two or more hydroxy groups bonded to the ring in the same molecule. The simplest examples are the three benzenediols, each having two groups on a benzene ring. Organisms that synthesize phenolic compounds do so in response to pressures such as pathogen and insect attack, UV radiation. As they are present in food consumed in human diets and in used in traditional medicine of several cultures, their role in human health. Some phenols are germicidal and are used in formulating disinfectants, others possess estrogenic or endocrine disrupting activity. They can also be classified on the basis of their number of phenol groups and they can therefore be called simple phenols or monophenols, with only one phenolic group, or di-, tri- and oligophenols, with two, three or several phenolic groups respectively. The phenolic unit can be found dimerized or further polymerized, creating a new class of polyphenol, two natural phenols from two different categories, for instance a flavonoid and a lignan, can combine to form a hybrid class like the flavonolignans. Nomenclature of polymers, Plants in the genus Humulus and Cannabis produce terpenophenolic metabolites, phenolic lipids are long aliphatic chains bonded to a phenolic moiety. The majority of compounds are solubles molecules but the smaller molecules can be volatiles. Many natural phenols present chirality within their molecule, an example of such molecules is catechin. Cavicularin is an unusual macrocycle because it was the first compound isolated from nature displaying optical activity due to the presence of planar chirality, natural phenols chemically interact with many other substances. Stacking, a property of molecules with aromaticity, is seen occurring between phenolic molecules. When studied in mass spectrometry, phenols easily form adduct ions with halogens and they can also interact with the food matrices or with different forms of silica
