1.
Drug nomenclature
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Drug nomenclature is the systematic naming of drugs, especially pharmaceutical drugs. Generic names for drugs are nowadays constructed out of affixes and stems that classify the drugs into different categories, a marketed drug might also have a company code or compound code. The chemical names are the names, based on the molecular structure of the drug. There are various systems of nomenclature and thus various chemical names for any one substance. The most important is the IUPAC name, chemical names are typically very long and too complex to be commonly used in referring to a drug. Sometimes, a company that is developing a drug might give the drug a company code, for example, CDP870 is UCB’s company code for Cimzia. Many of these codes, although not all, have prefixes that correspond to the company name, during development, the company will apply for regulatory approval of the drug by the relevant national regulatory agency, and it will apply for a generic name for that country. It will also apply for an International Nonproprietary Name through the World Health Organization, nowadays the national nonproprietary names are usually the same as the INN. The generic names usually indicate via their stems what drug class the drug belongs to, for example, one can tell that aciclovir is an antiviral drug because its name ends in the -vir suffix. Otherwise the 2 names are both given, joined by hyphens or slashes. For example, suspensions combining trimethoprim and sulfamethoxazole are called either trimethoprim/sulfamethoxazole or co-trimoxazole, similarly, co-codamol is codeine-acetaminophen, and co-triamterzide is triamterene-hydrochlorothiazide. The USP ceased maintaining PENs, but the similar co-prefixed BANs are still current, for drugs that make it all the way through development, testing, and regulatory acceptance, the pharmaceutical company then gives the drug a trade name. The term trade name is a term in the pharmaceutical industry for a brand name or trademark name. For example, Lipitor is Pfizers trade name for atorvastatin, a cholesterol-lowering medication, Drug names are often subject to legal regulation, including approval for new drugs and on packaging to establish clear rules about adulterants and fraudulent or misleading labelling. A national formulary is often designated to define drug names for regulatory purposes, unbiased mentions of a drug place the nonproprietary name first and follow it with the trade name in parentheses, if relevant. This pattern is important for the literature, where conflict of interest is disclosed or avoided. The authors reporting on a study are not endorsing any particular brand of drug and they will often state which brand was used, for methodologic validity, but they do so in a way that makes clear the absence of endorsement. For example, the 2015 American Society of Hematology publication policies say, Non-proprietary names should be used and he first letter of the name of a proprietary drug should be capitalized
2.
Corticosteroid
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Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Some common naturally occurring steroid hormones are cortisol, corticosterone, cortisone and aldosterone, the main corticosteroids produced by the adrenal cortex are cortisol and aldosterone. Glucocorticoids such as cortisol affect carbohydrate, fat, and protein metabolism, and have anti-inflammatory, immunosuppressive, anti-proliferative, anti-inflammatory effects are mediated by blocking the action of inflammatory mediators and inducing anti-inflammatory mediators. Immunosuppressive effects are mediated by suppressing delayed hypersensitivity reactions by direct action on T-lymphocytes, anti-proliferative effects are mediated by inhibition of DNA synthesis and epidermal cell turnover. Vasoconstrictive effects are mediated by inhibiting the action of inflammatory mediators such as histidine, synthetic pharmaceutical drugs with corticosteroid-like effects are used in a variety of conditions, ranging from brain tumors to skin diseases. Dexamethasone and its derivatives are almost pure glucocorticoids, while prednisone, hydrocortisone is typically used for replacement therapy, e. g. for adrenal insufficiency and congenital adrenal hyperplasia. Corticosteroids are also used supportively to prevent nausea, often in combination with 5-HT3 antagonists, typical undesired effects of glucocorticoids present quite uniformly as drug-induced Cushings syndrome. Typical mineralocorticoid side-effects are hypertension, hypokalemia, hypernatremia without causing peripheral edema, metabolic alkalosis, there may also be impaired wound healing or ulcer formation because of the immunosuppressive effects. Clinical and experimental evidence indicates that corticosteroids can cause permanent eye damage by inducing central serous retinopathy, a variety of steroid medications, from anti-allergy nasal sprays to topical skin creams, to eye drops, to prednisone have been implicated in the development of CSR. Corticosteroids have been used in treating people with traumatic brain injury. A systematic review identified 20 randomised controlled trials and included 12,303 participants, the authors recommended people with traumatic head injury should not be routinely treated with corticosteroids. There is some basis for genetic variation in response to inhaled corticosteroids. Two genes of interest are CHRH1 and TBX21, both genes display some degree of polymorphic variation in humans, which may explain how some patients respond better to inhaled corticosteroid therapy than others. Use of corticosteroids has numerous side-effects, some of which may be severe, Neuropsychiatric, steroid psychosis, therapeutic doses may cause a feeling of artificial well-being. The neuropsychiatric effects are mediated by sensitization of the body to the actions of adrenaline. Therapeutically, the bulk of corticosteroid dose is given in the morning to mimic the bodys diurnal rhythm, if given at night, an extensive review is provided by Flores and Gumina. Cardiovascular, Corticosteroids can cause sodium retention through an action on the kidney. This can result in retention and hypertension
3.
Glucocorticoid
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Glucocorticoids are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the receptor, that is present in almost every vertebrate animal cell. The name glucocorticoid is composed from its role in regulation of metabolism, synthesis in the adrenal cortex. A less common synonym is glucocorticosteroid, gCs are part of the feedback mechanism in the immune system which reduces certain aspects of immune function, such as reduction of inflammation. They are therefore used in medicine to treat diseases caused by an immune system, such as allergies, asthma, autoimmune diseases. GCs have many effects, including potentially harmful side effects. They also interfere with some of the mechanisms in cancer cells. This includes, inhibitory effects on lymphocyte proliferation as in the treatment of lymphomas and leukemias, gCs affect cells by binding to the glucocorticoid receptor. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by their specific receptors, target cells, in technical terms, corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids are chiefly produced in the zona fasciculata of the adrenal cortex, cortisol is the most important human glucocorticoid. It is essential for life, and it regulates or supports a variety of important cardiovascular, metabolic, immunologic, glucocorticoid effects may be broadly classified into two major categories, immunological and metabolic. In addition, glucocorticoids play important roles in development and body fluid homeostasis. As discussed in detail below, glucocorticoids function through interaction with the glucocorticoid receptor. Down-regulate the expression of proinflammatory proteins, glucocorticoids are also shown to play a role in the development and homeostasis of T lymphocytes. This has been shown in mice with either increased or decreased sensitivity of T cell lineage to glucocorticoids. The name glucocorticoid derives from early observations that these hormones were involved in glucose metabolism, in the fasted state, cortisol stimulates several processes that collectively serve to increase and maintain normal concentrations of glucose in blood. Enhancing the expression of enzymes involved in gluconeogenesis is probably the best-known metabolic function of glucocorticoids, mobilization of amino acids from extrahepatic tissues, These serve as substrates for gluconeogenesis. Excessive glucocorticoid levels resulting from administration as a drug or hyperadrenocorticism have effects on many systems, some examples include inhibition of bone formation, suppression of calcium absorption, delayed wound healing, muscle weakness, and increased risk of infection
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.
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
6.
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
7.
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
8.
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
9.
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
10.
Organic compound
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An organic compound is virtually any chemical compound that contains carbon, although a consensus definition remains elusive and likely arbitrary. Organic compounds are rare terrestrially, but of importance because all known life is based on organic compounds. The most basic petrochemicals are considered the building blocks of organic chemistry, for historical reasons discussed below, a few types of carbon-containing compounds, such as carbides, carbonates, simple oxides of carbon, and cyanides are considered inorganic. The distinction between organic and inorganic compounds, while useful in organizing the vast subject of chemistry. Organic chemistry is the science concerned with all aspects of organic compounds, Organic synthesis is the methodology of their preparation. The word organic is historical, dating to the 1st century, for many centuries, Western alchemists believed in vitalism. This is the theory that certain compounds could be synthesized only from their classical elements—earth, water, air, vitalism taught that these organic compounds were fundamentally different from the inorganic compounds that could be obtained from the elements by chemical manipulation. Vitalism survived for a while even after the rise of modern atomic theory and it first came under question in 1824, when Friedrich Wöhler synthesized oxalic acid, a compound known to occur only in living organisms, from cyanogen. A more decisive experiment was Wöhlers 1828 synthesis of urea from the inorganic salts potassium cyanate, urea had long been considered an organic compound, as it was known to occur only in the urine of living organisms. Wöhlers experiments were followed by others, in which increasingly complex organic substances were produced from inorganic ones without the involvement of any living organism. Even though vitalism has been discredited, scientific nomenclature retains the distinction between organic and inorganic compounds, still, even the broadest definition requires excluding alloys that contain carbon, including steel. The C-H definition excludes compounds that are considered organic, neither urea nor oxalic acid is organic by this definition, yet they were two key compounds in the vitalism debate. The IUPAC Blue Book on organic nomenclature specifically mentions urea and oxalic acid, other compounds lacking C-H bonds but traditionally considered organic include benzenehexol, mesoxalic acid, and carbon tetrachloride. Mellitic acid, which contains no C-H bonds, is considered an organic substance in Martian soil. The C-H bond-only rule also leads to somewhat arbitrary divisions in sets of carbon-fluorine compounds, for example, CF4 would be considered by this rule to be inorganic, whereas CF3H would be organic. Organic compounds may be classified in a variety of ways, one major distinction is between natural and synthetic compounds. Another distinction, based on the size of organic compounds, distinguishes between small molecules and polymers, natural compounds refer to those that are produced by plants or animals. Many of these are extracted from natural sources because they would be more expensive to produce artificially
11.
International Standard Book Number
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The International Standard Book Number is a unique numeric commercial book identifier. An ISBN is assigned to each edition and variation of a book, for example, an e-book, a paperback and a hardcover edition of the same book would each have a different ISBN. The ISBN is 13 digits long if assigned on or after 1 January 2007, the method of assigning an ISBN is nation-based and varies from country to country, often depending on how large the publishing industry is within a country. The initial ISBN configuration of recognition was generated in 1967 based upon the 9-digit Standard Book Numbering created in 1966, the 10-digit ISBN format was developed by the International Organization for Standardization and was published in 1970 as international standard ISO2108. Occasionally, a book may appear without a printed ISBN if it is printed privately or the author does not follow the usual ISBN procedure, however, this can be rectified later. Another identifier, the International Standard Serial Number, identifies periodical publications such as magazines, the ISBN configuration of recognition was generated in 1967 in the United Kingdom by David Whitaker and in 1968 in the US by Emery Koltay. The 10-digit ISBN format was developed by the International Organization for Standardization and was published in 1970 as international standard ISO2108, the United Kingdom continued to use the 9-digit SBN code until 1974. The ISO on-line facility only refers back to 1978, an SBN may be converted to an ISBN by prefixing the digit 0. For example, the edition of Mr. J. G. Reeder Returns, published by Hodder in 1965, has SBN340013818 -340 indicating the publisher,01381 their serial number. This can be converted to ISBN 0-340-01381-8, the check digit does not need to be re-calculated, since 1 January 2007, ISBNs have contained 13 digits, a format that is compatible with Bookland European Article Number EAN-13s. An ISBN is assigned to each edition and variation of a book, for example, an ebook, a paperback, and a hardcover edition of the same book would each have a different ISBN. The ISBN is 13 digits long if assigned on or after 1 January 2007, a 13-digit ISBN can be separated into its parts, and when this is done it is customary to separate the parts with hyphens or spaces. Separating the parts of a 10-digit ISBN is also done with either hyphens or spaces, figuring out how to correctly separate a given ISBN number is complicated, because most of the parts do not use a fixed number of digits. ISBN issuance is country-specific, in that ISBNs are issued by the ISBN registration agency that is responsible for country or territory regardless of the publication language. Some ISBN registration agencies are based in national libraries or within ministries of culture, in other cases, the ISBN registration service is provided by organisations such as bibliographic data providers that are not government funded. In Canada, ISBNs are issued at no cost with the purpose of encouraging Canadian culture. In the United Kingdom, United States, and some countries, where the service is provided by non-government-funded organisations. Australia, ISBNs are issued by the library services agency Thorpe-Bowker
12.
Natural product
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A natural product is a chemical compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life, natural products can also be prepared by chemical synthesis and have played a central role in the development of the field of organic chemistry by providing challenging synthetic targets. The term natural product has also extended for commercial purposes to refer to cosmetics, dietary supplements. Within the field of chemistry, the definition is often further restricted to secondary metabolites. Secondary metabolites are not essential for survival, but nevertheless provide organisms that produce them an evolutionary advantage, many secondary metabolites are cytotoxic and have been selected and optimized through evolution for use as chemical warfare agents against prey, predators, and competing organisms. Natural products sometimes have pharmacological or biological activity that can be of benefit in treating diseases. As such, natural products are the active components not only of most traditional medicines, in fact, natural products are the inspiration for approximately one half of U. S. Food and Drug Administration-approved drugs. The broadest definition of natural product is anything that is produced by life, and includes the likes of biotic materials, bio-based materials, bodily fluids, a more restrictive definition of a natural product is an organic compound that is synthesized by a living organism. The remainder of this article restricts itself to this more narrow definition, natural products may be classified according to their biological function, biosynthetic pathway, or source as described below. Following Albrecht Kossels original proposal in 1891, natural products are divided into two major classes, the primary and secondary metabolites. Primary metabolites have a function that is essential to the survival of the organism that produces them. Secondary metabolites in contrast have a function that mainly affects other organisms. Secondary metabolites are not essential to survival but do increase the competitiveness of the organism within its environment, because of their ability to modulate biochemical and signal transduction pathways, some secondary metabolites have useful medicinal properties. Natural products especially within the field of chemistry are often defined as primary and secondary metabolites. A more restrictive definition limiting natural products to secondary metabolites is commonly used within the fields of medicinal chemistry, primary metabolites as defined by Kossel are components of basic metabolic pathways that are required for life. They are associated with cellular functions such as nutrient assimilation, energy production. They have a species distribution that span many phyla and frequently more than one kingdom. Primary metabolites include carbohydrates, lipids, amino acids, and nucleic acids which are the building blocks of life
13.
Cortisone acetate
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Cortisone, also known as 17α, 21-dihydroxypregn-4-ene-3,11, 20-trione, is a pregnane steroid hormone. It is one of the main hormones released by the adrenal gland in response to stress, in chemical structure, it is a corticosteroid closely related to cortisol. It is used to treat a variety of ailments and can be administered intravenously, orally, intraarticularly, cortisone suppresses the immune system, thus reducing inflammation and attendant pain and swelling at the site of the injury. Risks exist, in particular in the use of cortisone. Cortisone, a glucocorticoid, and adrenaline are the main hormones released by the body as a reaction to stress and they elevate blood pressure and prepare the body for a fight or flight response. Cortisone may also be used to suppress immune response in persons with autoimmune diseases or following an organ transplant to prevent transplant rejection. The suppression of the system may also be important in the treatment of inflammatory conditions. Cortisone is a treatment for a severe sore throat that occurs commonly with EBV infectious mononucleosis. Cortisone is also used by dermatologists to treat keloids, relieve the symptoms of eczema and atopic dermatitis, local side effects are rare but can include, pain, infection, skin pigment changes, loss of fatty tissue, and tendon rupture. Cortisone was first identified by the American chemists Edward Calvin Kendall, as it turns out, both Reichstein and the team of O. Wintersteiner and J. Pfiffner had separately isolated the compound prior to Mason/Kendall, but failed to recognize its biological significance. Dr. Masons contributions to the crystallization and characterization of the compound have generally been forgotten outside of the Mayo Clinic, cortisone was first produced commercially by Merck & Co. On September 30,1949, Percy Julian announced an improvement in the process of producing cortisone from bile acids and this eliminated the need to use osmium tetroxide, a rare, expensive, and dangerous chemical. In the UK in the early 1950s, John Cornforth and Kenneth Callow at the National Institute for Medical Research collaborated with Glaxo to produce cortisone from hecogenin from sisal plants, cortisone is one of several end-products of a process called steroidogenesis. This process starts with the synthesis of cholesterol, which proceeds through a series of modifications in the adrenal gland to become any one of many steroid hormones. One end-product of this pathway is cortisol, for cortisol to be released from the adrenal gland, a cascade of signaling occurs. Corticotropin-releasing hormone released from the hypothalamus stimulates corticotrophs in the pituitary to release ACTH. Here, the zona fasciculata and zona reticularis, in response to ACTH, secrete glucocorticoids, in the peripheral tissues, cortisol is converted to cortisone by the enzyme 11-beta-steroid dehydrogenase. Cortisone has marginally reduced glucocorticoid activity compared to cortisol, and thus, however, 11-beta-steroid dehydrogenase can catalyze the reverse reaction as well, and, thus, cortisone is also a precursor molecule of cortisol
14.
11-Deoxycortisol
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11-Deoxycortisol, also known as cortodoxone or cortexolone, as well as 17α, 21-dihydroxyprogesterone or 17α, 21-dihydroxypregn-4-ene-3, 20-dione, is a glucocorticoid steroid hormone. It was first synthesized by Tadeusz Reichstein, and has also referred to as Reichsteins Substance. 11α-oxygenation of Compound S produces 11α-hydrocortisone, which can be oxidized to cortisone. 11-Deoxycortisol acts as a glucocorticoid, though is less potent than cortisol and it can be synthesized from 17α-hydroxyprogesterone. In 11β-hydroxylase deficiency, 11-deoxycortisol levels increase dramatically, causing hypertension, 11-Deoxycortisol can also be converted to androstenedione. This could explain, at least in part, the increase in androstenedione levels in 11β-hydroxylase deficiency
15.
11-Deoxycorticosterone
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As its names indicate, 11-deoxycorticosterone can be understood as the 21-hydroxy- variant of progesterone or as the 11-deoxy- variant of corticosterone. DOC is a potent mineralocorticoid but is devoid of glucocorticoid activity. However, 11β-hydroxylation of DOC produces corticosterone and confers glucocorticoid activity, in addition to its mineralocorticoid activity, DOC has been found to possess one-third to one-tenth the potency of progesterone as a progestogen when administered systematically to rabbits. However, it has no such activity when applied directly to the mucosa of mice. The discrepancy may be related to the fact that DOC can be converted into progesterone in vivo, DOC is a precursor molecule for the production of aldosterone. The major pathway for production is in the adrenal glomerulosa zone of the adrenal gland. It is not a major secretory hormone and it is produced from progesterone by 21β-hydroxylase and is converted to corticosterone by 11β-hydroxylase. Corticosterone is then converted to aldosterone by aldosterone synthase, most of the DOC is secreted by the zona fasciculata of the adrenal cortex which also secretes cortisol, and a small amount by the zona glomerulosa, which secretes aldosterone. DOC stimulates the collecting tubules to continue to excrete potassium in much the way that aldosterone does. At the same time it is not nearly so rigorous at retaining sodium as aldosterone and this hormone may be the peptide hormone kallikrein, which is augmented by DOC and suppressed by aldosterone. If sodium becomes very high, DOC also increases urine flow, DOC has about 1/20 of the sodium retaining power of aldosterone, and is said to be as little as one per cent of aldosterone at high water intakes. Since DOC has about 1/5 the potassium excreting power of aldosterone, dOCs injections do not cause much additional potassium excretion when sodium intake is low. This is probably because aldosterone is already stimulating potassium outflow, when sodium is low DOC probably would not have to be present, but when sodium rises aldosterone declines considerably, and DOC probably tends to take over. DOC has a feedback with respect to potassium as aldosterone. A rise in serum potassium causes a rise in DOC secretion, however, sodium has little effect, and what effect it does have is direct. Angiotensin has little effect on DOC, but DOC causes a fall in renin, and therefore angiotensin I. Therefore, DOC must be indirectly inhibiting aldosterone since aldosterone depends on angiotensin II, sodium, and therefore blood volume, is difficult to regulate internally. That is, when a large dose of sodium threatens the body with blood pressure
16.
Pregnenolone
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In addition, pregnenolone is biologically active in its own right, acting as a neurosteroid. This conversion involves hydroxylation of the chain at the C20 and C22 positions. To assay conversion of cholesterol to pregnenolone, radiolabelled cholesterol has been used, Pregnenolone product can be separated from cholesterol substrate using Sephadex LH-20 minicolumns. Pregnenolone is produced mainly in the gonads, adrenal glands, Pregnenolone undergoes further steroid metabolism in one of several ways, Pregnenolone can be converted into progesterone. The critical enzyme step is two-fold using a 3β-hydroxysteroid dehydrogenase and a Δ5-4 isomerase, the latter transfers the double bond from C5 to C4 on the A ring. Progesterone is the entry into the Δ4 pathway, resulting in production of 17α-hydroxyprogesterone and androstenedione, aldosterone and corticosteroids are also derived from progesterone or its derivatives. Pregnenolone can be converted to 17α-hydroxypregnenolone by the enzyme 17α-hydroxylase, using this pathway, termed Δ5 pathway, the next step is conversion to dehydroepiandrosterone via 17, 20-lyase. DHEA is the precursor of androstenedione, Pregnenolone can be converted to androstadienol by 16-ene synthase. Pregnenolone can be converted to sulfate by steroid sulfotransferase. Neurosteroids affect synaptic functioning, are neuroprotective, and enhance myelinization, Pregnenolone and its sulfate ester are under investigation for their potential to improve cognitive and memory functioning. Pregnenolone is also being considered as a treatment for schizophrenia. In addition, pregnenolone sulfate has been shown to activate the transient receptor potential M3 ion channel in hepatocytes and pancreatic islets causing calcium entry, Pregnenolone is involved in a natural negative feedback loop against CB1 receptor activation in animals. In contrast to pregnenolone, pregnenolone sulfate did not bind to microtubules, however, progesterone did and with similar affinity to pregnenolone, although unlike pregnenolone, it did not increase binding of MAP2 to tubulin. Pregnenolone was found to induce tubule polymerization in neuronal cultures and to increase growth in PC12 cells treated with nerve growth factor. As such, pregnenolone may control formation and stabilization of microtubules in neurons, Pregnenolone has been found to act as an agonist of the pregnane X receptor. This is in accordance with findings on the conversion of DHEA into testosterone, sripada et al. reported that oral pregnenolone is preferentially metabolized into the neurosteroid allopregnanolone rather than into other steroids such as DHEA or cortisol. Pregnanolone levels increased by approximately 60% while DHEA levels decreased non-significantly by approximately 5%, another study found that allopregnanolone levels were increased by 3-fold at 2 hours post-administration following a single 400 mg oral dose of pregnenolone. In addition to allopregnanolone, exogenous pregnenolone also functions as a prohormone of pregnenolone sulfate, Pregnenolone is lipophilic and readily crosses the blood-brain-barrier
17.
Chloroprednisone
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Chloroprednisone is a topical glucocorticoid first reported in 1960. It is a derivative of prednisone. The acetate ester prodrug, chloroprednisone 21-acetate, was sold under the brand name Topilan as an anti-inflammatory agent, there is little published about chloroprednisone. This may be due to limited activity topically because the skin lacks the necessary activating enzyme 11-Beta hydroxysteroid dehydrogenase, systemically, this agents activity on Glucocorticoid receptors may not have competed with agents like Fludrocortisone or Dexamethasone
18.
Fludrocortisone
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Fludrocortisone, sold under the brand name Florinef among others, is a corticosteroid used to treat adrenogenital syndrome, postural hypotension, and adrenal insufficiency. In adrenal insufficiency it is taken together with hydrocortisone. Common side effects include blood pressure, swelling, heart failure. Other serious side effects include low immune system function, cataracts, muscle weakness and it is unclear if use during pregnancy is safe for the baby. Fludrocortisone is mostly a mineralocorticoid, however, also has glucocorticoid effects and it is on the World Health Organizations List of Essential Medicines, the most effective and safe medicines needed in a health system. In the United Kingdom it costs the NHS about 1.52 pounds per month, in the United States the wholesale cost of a month of medications is about 11.96 USD. Fludrocortisone has been used in the treatment of cerebral salt wasting syndrome and it is used primarily to replace the missing hormone aldosterone in various forms of adrenal insufficiency such as Addisons disease and the classic salt wasting form of congenital adrenal hyperplasia. Due to its effects on increasing Na+ levels, and therefore blood volume, fludrocortisone is the first line of treatment for orthostatic intolerance and it can be used to treat low blood pressure. Fludrocortisone is also a confirmation test for diagnosing Conns syndrome, the fludrocortisone suppression test, loading the patient with fludrocortisone would suppress serum aldosterone level in a normal patient, whereas the level will not be altered in a Conns patient. Chemically, fludrocortisone is identical to cortisol except for the substitution of fluorine in place of one hydrogen, fluorine is a good bioisostere for hydrogen because it is similar in size. The major difference is in its electronegativity
19.
Fluocinolone
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Fluocinolone acetonide is a corticosteroid primarily used in dermatology to reduce skin inflammation and relieve itching. It is a synthetic hydrocortisone derivative, the fluorine substitution at position 9 in the steroid nucleus greatly enhances its activity. It was first synthesized in 1959 in the Research Department of Syntex Laboratories S. A, preparations containing it were first marketed under the name Synalar. A typical dosage strength used in dermatology is 0. 01–0. 025%, one such cream is sold under the brand name Flucort-N and includes the antibiotic neomycin. Fluocinolone acetonide intravitreal implants have been used to treat non-infectious uveitis, a systematic review could not determine whether fluocinolone acetonide implants are superior to standard of care treatment for uveitis. Flucinolone is a group V or group VI corticosteroid under US classification
20.
Tixocortol pivalate
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It has anti-inflammatory properties similar to hydrocortisone. It is marketed under the brand name Pivalone and it is sometimes used in patch testing in atopic dermatitis
21.
Betamethasone
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It can be taken by mouth, injected into a muscle, or applied as a cream. When given by injection, anti-inflammatory effects begin in two hours and last for seven days. Serious side effects include a risk of infection, muscle weakness, severe allergic reactions. Long-term use may cause adrenal insufficiency, stopping the medication suddenly following long-term use may be dangerous. The cream commonly results in increased growth and skin irritation. Betamethasone belongs to the class of medication. Betamethasone was approved for use in the United States in 1961. The cream is on the World Health Organizations List of Essential Medicines and it is available as a generic medication. In the United States the pills and injectable solution are expensive while the cream is not, betamethasone is a corticosteroid that is available as pill, by injection, and as a cream. It is used as a cream to relieve skin irritation. It is used as a treatment for psoriasis, as betamethasone dipropionate and salicylic acid. Betamethasone sodium phosphate is used orally and via injection with the same indications as other steroids, many betamethasone-based pharmaceuticals include the steroid as the valerate ester. In a randomized controlled trial betamethasone was shown to some of the ataxia symptoms associated with ataxia telangiectasia by 28-31%. Betamethasone is also used to stimulate fetal lung maturation, and to decrease the incidence, a cream with 0. 05% betamethasone appears effective in treating phimosis in boys, and often averts the need for circumcision. It has replaced circumcision as the treatment method for some physicians in the British National Health Service. Betamethasone is also used prior to delivery of a baby to help prepare the lungs for breathing. When injected into the space or the spine, it may cause serious side effects like loss of vision, stroke. Betamethasone is available in a number of forms, betamethasone dipropionate, betamethasone sodium phosphate
