3,5-Dihydroxy-4-isopropyl-trans-stilbene
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3,5-dihydroxy-4-isopropyl-trans-stilbene
Tapinarof, also known as benvitimod and sold under the brand name Vtama, is a medication used for the treatment of plaque psoriasis. The medication is applied to the skin. Besides its use in medicine, tapinarof is a naturally occurring compound found in bacterial symbionts of nematodes which has antibiotic properties. The medication acts as an aryl hydrocarbon receptor agonist. Tapinarof was approved for medical use in the United States in May 2022. Medical uses Tapinarof is indicated for the treatment of plaque psoriasis in adults. Society and culture Names Tapinarof is the International Nonproprietary Name (INN). Natural occurrence Tapinarof, also known as benvitimod, is a bacterial stilbenoid produced in '' Photorhabdus'' bacterial symbionts of ''Heterorhabditis'' nematodes. It is a product of an alternative ketosynthase-directed stilbenoid biosynthesis pathway. It is derived from the condensation of two β-ketoacyl thioesters. It is produced by the '' Photorhabdus lu ...
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Topical Administration
A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes including creams, foams, gels, lotions, and ointments. Many topical medications are epicutaneous, meaning that they are applied directly to the skin. Topical medications may also be inhalational, such as asthma medications, or applied to the surface of tissues other than the skin, such as eye drops applied to the conjunctiva, or ear drops placed in the ear, or medications applied to the surface of a tooth. The word ''topical'' derives from Greek τοπικός ''topikos'', "of a place". Justification Topical drug delivery is a route of administering drugs via the skin to provide topical therapeutic effects. As skin is one of the largest and most superficial organs in the human body, pharmacists utilise it to deliver various drugs. This ...
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Entomopathogenic Nematode (Heterorhabditis Bacteriophora ) Poinar, 1975
Entomopathogenic nematodes (EPN) are a group of nematodes (thread worms), that cause death to insects. The term ''entomopathogenic'' has a Greek origin, with ''entomon'', meaning ''insect'', and ''pathogenic'', which means ''causing disease''. They are animals that occupy a bio control middle ground between microbial pathogens and predator/parasitoids. Although many other parasitic thread worms cause diseases in living organisms (sterilizing or otherwise debilitating their host), entomopathogenic nematodes are specific in only infecting insects. Entomopathogenic nematodes (EPNs) live parasitically inside the infected insect host, and so they are termed as ''endoparasitic''. They infect many different types of insects living in the soil like the larval forms of moths, butterflies, flies and beetles as well as adult forms of beetles, grasshoppers and crickets. EPNs have been found in all over the world and a range of ecologically diverse habitats. They are highly diverse, complex and ...
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Pinosylvin
Pinosylvin is an organic compound with the formula C6H5CH=CHC6H3(OH)2. A white solid, it is related to trans-stilbene, but with two hydroxy groups on one of the phenyl substituents. It is very soluble in many organic solvents, such as acetone. Occurrence Pinosylvin is produced in plants in response to fungal infections, ozone-induced stress, and physical damage for example. It is a fungitoxin protecting the wood from fungal infection. It is present in the heartwood of ''Pinaceae'' and also found in '' Gnetum cleistostachyum''. Injected in rats, pinosylvin undergoes rapid glucuronidation and a poor bioavailability. Biosynthesis Pinosylvin synthase, an enzyme, catalyzes the biosynthesis of pinosylvin from malonyl-CoA and cinnamoyl-CoA: :3 malonyl-S-CoA + cinnamoyl-S-CoA → 4 CoA-SH + pinosylvin + 4 CO2 This biosynthesis is noteworthy because plant biosyntheses employing cinnamic acid as a starting point are rare compared to the more common use of ''p''-coumaric acid. Tw ...
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Galleria Mellonella
''Galleria mellonella'', the greater wax moth or honeycomb moth, is a moth of the family Pyralidae. ''G. mellonella'' is found throughout the world. It is one of two species of wax moths, with the other being the lesser wax moth. ''G. mellonella'' eggs are laid in the spring, and they have four life stages. Males are able to generate ultrasonic sound pulses, which, along with pheromones, are used in mating. The larvae of ''G. mellonella'' are also often used as a model organism in research. The greater wax moth is well known for its Parasitism, parasitization of honeybees and their hives. Because of the economic loss caused by this species, several control methods including heat treatment and chemical fumigants such as carbon dioxide have been used. The caterpillar of ''G. mellonella'' has attracted interest for its ability to degrade Polyethylene, polyethylene plastic. Geographic range ''G. mellonella'' was first reported as a pest in Asia, but then spread to northern Africa ...
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Heterorhabditis Megidis
''Heterorhabditis megidis'' is a species of nematodes in the genus ''Heterorhabditis''. All species of this genus are obligate parasites of insects, and some are used as biological control agents for the control of pest insects. ''Heterorhabditis megidis'' nematodes are hosts for the '' Photorhabdus luminescens'' bacterial symbiont. It can be used to fight the Japanese beetle, ''Popillia japonica'' (Scarabaeidae: Coleoptera), in Ohio. 3,5-Dihydroxy-4-isopropyl-''trans''-stilbene is a bacterial stilbenoid produced by the ''P. luminescens'' bacterial symbiont species of the entomopathogenic nematode, ''H. megidis''. Experiments with infected larvae of ''Galleria mellonella ''Galleria mellonella'', the greater wax moth or honeycomb moth, is a moth of the family Pyralidae. ''G. mellonella'' is found throughout the world. It is one of two species of wax moths, with the other being the lesser wax moth. ''G. mellonella' ...'', the wax moth, support the hypothesis that the compound h ...
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Photorhabdus Luminescens
''Photorhabdus luminescens'' (previously called ''Xenorhabdus luminescens'') is a Gammaproteobacterium of the family Morganellaceae, and is a lethal pathogen of insects. It lives in the gut of an entomopathogenic nematode of the family Heterorhabditidae. When the nematode infects an insect, ''P. luminescens'' is released into the blood stream and rapidly kills the insect host (within 48 hours) by producing toxins, such as the high molecular weight insecticidal protein complex Tca. ''P. luminescens'' also produces a proteic toxin through the expression of a single gene called ''makes caterpillars floppy'' (mcf). It also secretes enzymes which break down the body of the infected insect and bioconvert it into nutrients which can be used by both nematode and bacteria. In this way, both organisms gain enough nutrients to replicate (or reproduce in the case of the nematode) several times. The bacteria enter the nematode progeny as they develop. 3,5-Dihydroxy-4-isopropyl-trans-stilb ...
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Thioester
In organic chemistry, thioesters are organosulfur compounds with the functional group . They are analogous to carboxylate esters () with the sulfur in the thioester playing the role of the linking oxygen in the carboxylate ester, as implied by the ''thio-'' prefix. They are the product of esterification between a carboxylic acid () and a thiol (). In biochemistry, the best-known thioesters are derivatives of coenzyme A, e.g., acetyl-CoA.Matthys J. Janssen "Carboxylic Acids and Esters" in PATAI's Chemistry of Functional Groups: Carboxylic Acids and Esters, Saul Patai, Ed. John Wiley, 1969, New York: pp. 705–764. Synthesis The most typical route to thioester involves the reaction of an acid chloride with an alkali metal salt of a thiol: :RSNa + R'COCl -> R'COSR + NaCl Another common route entails the displacement of halides by the alkali metal salt of a thiocarboxylic acid. For example, thioacetate esters are commonly prepared by alkylation of potassium thioacetate: :CH3COSK + ...
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Condensation Reaction
In organic chemistry, a condensation reaction is a type of chemical reaction in which two molecules are combined to form a single molecule, usually with the loss of a small molecule such as water. If water is lost, the reaction is also known as a dehydration synthesis. However other molecules can also be lost, such as ammonia, ethanol, acetic acid and hydrogen sulfide. The addition of the two molecules typically proceeds in a step-wise fashion to the addition product, usually in equilibrium, and with loss of a water molecule (hence the name condensation). The reaction may otherwise involve the functional groups of the molecule, and is a versatile class of reactions that can occur in acidic or basic conditions or in the presence of a catalyst. This class of reactions is a vital part of life as it is essential to the formation of peptide bonds between amino acids and to the biosynthesis of fatty acids. Many variations of condensation reactions exist. Common examples include the ...
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Ketosynthase
Ketoacyl synthases (KSs) catalyze the condensation reaction of acyl-CoA or acyl-acyl ACP with malonyl-CoA to form 3-ketoacyl-CoA or with malonyl-ACP to form 3-ketoacyl-ACP. This reaction is a key step in the fatty acid synthesis cycle, as the resulting acyl chain is two carbon atoms longer than before. KSs exist as individual enzymes, as they do in type II fatty acid synthesis and type II polyketide synthesis, or as domains in large multidomain enzymes, such as type I fatty acid synthases (FASs) and polyketide synthases (PKSs). KSs are divided into five families: KS1, KS2, KS3, KS4, and KS5. Multidomain enzyme systems Fatty acid synthase Fatty acid synthase (FAS) is the enzyme system involved in de novo fatty acid synthesis. FAS is an iterative multienzyme consisting of several component enzymes, one of which is ketoacyl synthase. There are two types of FASs: type I and type II. Type I FASs are highly integrated multidomain enzymes. They contain discrete functional domains respo ...
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Heterorhabditis
''Heterorhabditis'' is a genus of nematodes belonging to the order Rhabditida. All species of this genus are obligate parasites of insects, and some are used as biological control agents for the control of pest insects. ''Heterorhabditis'' nematodes are hosts for the '' Photorhabdus'' bacterial symbiont. Species The recognized species in this genus are: * '' Heterorhabditis amazonensis'' Andaló, Nguyen & Moino, 2007 * ''Heterorhabditis bacteriophora'' Poinar, 1976 * '' Heterorhabditis baujardi'' Phan, Subbotin, Nguyen & Moens, 2003 * '' Heterorhabditis downesi'' Stock, Griffin & Burnell, 2002 * '' Heterorhabditis floridensis'' Nguyen, Gozel, Koppenhöfer & Adams, 2006 * '' Heterorhabditis georgiana'' Nguyen, Shapiro-Ilan and Mbata, 2008 * '' Heterorhabditis heliothidis'' (Khan, Brooks & Hirschmann, 1976) * '' Heterorhabditis indica'' Poinar, Karunakar & David, 1992 * '' Heterorhabditis marelatus'' Liu & Berry, 1996 * ''Heterorhabditis megidis'' Poinar, Jackson & Klein, 1987 * '' ...
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Photorhabdus
''Photorhabdus'' is a genus of bioluminescent, gram-negative bacilli which lives symbiotically within entomopathogenic nematodes, hence the name ''photo'' (which means light producing) and ''rhabdus'' (rod shape). ''Photorhabdus'' is known to be pathogenic to a wide range of insects and has been used as biopesticide in agriculture. Life cycle ''Photorhabdus'' species facilitate the reproduction of entomopathogenic nematodes by infecting and killing susceptible insect larvae. Entomopathogenic nematodes are normally found in soil. Nematodes infect larval hosts by piercing the larval cuticle. When the nematode enters an insect larvae, ''Photorhabdus'' species are released by the nematodes and will produce a range of toxins, killing the host within 48 hours. ''Photorhabdus'' species feed on the cadaver of the insect and the process converts the cadaver into a nutrient source for the nematode. Mature nematodes leave the depleted body of the insect and search for new hosts to infect. ...
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Stilbenoid
Stilbenoids are hydroxylated derivatives of stilbene. They have a C6–C2–C6 structure. In biochemical terms, they belong to the family of phenylpropanoids and share most of their biosynthesis pathway with chalcones. Most stilbenoids are produced by plants, and the only known exception is the antihelminthic and antimicrobial stilbenoid, 2-isopropyl-5- ''E'')-2-phenylvinylenzene-1,3-diol, biosynthesized by the Gram-negative bacterium '' Photorhabdus luminescens.'' Chemistry Stilbenoids are hydroxylated derivatives of stilbene and have a C6–C2–C6 structure. 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, called stilbene photocyclization to form dihydrophenanthrenes. Oligomeric forms are known as oligostilbenoids. Types ;Aglycones * Piceatannol in the roots of Norway spruces * Pinosylvin is a fungal toxin protecting wood f ...
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