Flavaglines are a family of natural products that are found in plants of the genus Aglaia (Meliaceae). These compounds are characterized by a cyclopenta[b]benzofuran skeleton. In 1982 King and colleagues discovered the first member of this family, rocaglamide, based on its antileukemic activity. [1] Since then, about 50 other flavaglines have been characterized. These molecules display strong insecticidal, antifungal, anti-inflammatory, neuroprotective, cardioprotective and anticancer activities. [2] [3] In mouse models of cancer, flavaglines enhance the efficacy of chemotherapies [4] [5] and also alleviate the cardiac adverse effect of these chemotherapies. [6]
The challenge raised by their structural complexity has attracted the attention of some organic chemists. In 1990, Barry Trost presented an enantioselective synthesis of rocaglamide in 18 steps and confirmed its absolute configuration. [7]
Combinatorial chemistry comprises chemical synthetic methods that make it possible to prepare a large number of compounds in a single process. These compound libraries can be made as mixtures, sets of individual compounds or chemical structures generated by computer software. Combinatorial chemistry can be used for the synthesis of small molecules and for peptides.
Aglaia is a genus of 117 species of woody dioecious trees belonging to the Mahogany family (Meliaceae). These trees occur in the subtropical and tropical forests of Southeast Asia, Northern Australia and the Pacific.
In chemical synthesis, click chemistry is a class of biocompatible small molecule reactions commonly used in bioconjugation, allowing the joining of substrates of choice with specific biomolecules. Click chemistry is not a single specific reaction, but describes a way of generating products that follow examples in nature, which also generates substances by joining small modular units. In many applications, click reactions join a biomolecule and a reporter molecule. Click chemistry is not limited to biological conditions: the concept of a "click" reaction has been used in chemoproteomic, pharmacological, and various biomimetic applications. However, they have been made notably useful in the detection, localization and qualification of biomolecules.
Organoborane or organoboron compounds are chemical compounds of boron and carbon that are organic derivatives of BH3, for example trialkyl boranes. Organoboron chemistry or organoborane chemistry is the chemistry of these compounds.
Tetrazoles are a class of synthetic organic heterocyclic compound, consisting of a 5-member ring of four nitrogen atoms and one carbon atom. The name tetrazole also refers to the parent compound with formula CH2N4, of which three isomers can be formulated.
Maltol is a naturally occurring organic compound that is used primarily as a flavor enhancer. It is found in the bark of larch tree, in pine needles, and in roasted malt. It is a white crystalline powder that is soluble in hot water, chloroform, and other polar solvents. Because it has the odor of cotton candy and caramel, maltol is used to impart a sweet aroma to fragrances. Maltol's sweetness adds to the odor of freshly baked bread, and is used as a flavor enhancer in breads and cakes.
Aglaia silvestris is a species of plant in the family Meliaceae. It is found in Cambodia, India, Indonesia, Malaysia, Papua New Guinea, the Philippines, the Solomon Islands, Thailand, and Vietnam. This plant initiated the naming of the Rocaglamide derivatives silvestrol and episilvestrol. In fact they were derived from the fruits and twigs of Aglaia foveolata.
Monoamine oxidase B, also known as MAOB, is an enzyme that in humans is encoded by the MAOB gene.
Dual specificity tyrosine-phosphorylation-regulated kinase 1A is an enzyme that in humans is encoded by the DYRK1A gene. Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or in the 3' coding region. These variants encode at least five different isoforms.
Thiostrepton is a natural cyclic oligopeptide antibiotic of the thiopeptide class, derived from several strains of streptomycetes, such as Streptomyces azureus and Streptomyces laurentii. Thiostrepton is a natural product of the ribosomally synthesized and post-translationally modified peptide (RiPP) class.
In organic chemistry, S-nitrosothiols, also known as thionitrites, are organic compounds or functional groups containing a nitroso group attached to the sulfur atom of a thiol. S-Nitrosothiols have the general formula R−S−N=O, where R denotes an organic group. Originally suggested by Ignarro to serve as intermediates in the action of organic nitrates, endogenous S-nitrosothiols were discovered by Stamler and colleagues and shown to represent a main source of NO bioactivity in vivo. More recently, S-nitrosothiols have been implicated as primary mediators of protein S-nitrosylation, the oxidative modification of cysteine thiol that provides ubiquitous regulation of protein function.
The Tsuji–Trost reaction is a palladium-catalysed substitution reaction involving a substrate that contains a leaving group in an allylic position. The palladium catalyst first coordinates with the allyl group and then undergoes oxidative addition, forming the π-allyl complex. This allyl complex can then be attacked by a nucleophile, resulting in the substituted product.
Aglaia duperreana is a species of plant in the family Meliaceae. It is a shrub or small tree with yellow flowers. Its origin is in Vietnam, but is now found throughout South East Asia.
Substituted tryptamines, or serotonin analogues, are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all tryptamines contain an indole ring, joined to an amino (NH2) group via an ethyl (−CH2–CH2−) sidechain. In substituted tryptamines, the indole ring, sidechain, and/or amino group are modified by substituting another group for one of the hydrogen (H) atoms.
FL3 is a synthetic flavagline that displays potent anticancer and cardioprotectant activities. This compound induces the death of cancer cells by an original mechanism that involves the apoptosis-inducing factor and caspase 12, suggesting that it may improve the efficacy of cancer chemotherapies. It was also shown that FL3 may enhance the efficacy of one of the most widely used anticancer agents, doxorubicin, and alleviate its main adverse effect, cardiac damage.
Rocaglamide is a natural product which belongs to a class of molecules called flavaglines. This compound was isolated in 1982 by King, Ming-Lu (金明儒) and colleagues based on its antileukemic activity. The name of Rocaglamide is named from two parts: Roc- and aglamide. Roc- means Republic of China(中華民國), the place in which this product isolated; aglamide indicates this product is isolated from Large-leaved Aglaia. Like other flavaglines, rocaglamide displays potent insecticidal, antifungal, anti-inflammatory and anticancer activities. Rocaglamide A (RocA) inhibits eukaryotic translation initiation by binding to the translation initiation factor eIF4A and converting it into a translational repressor.
Secalonic acids are a group of chiral dimeric tetrahydroxanthones closely related to ergoflavin and ergochrysin A that are collectively called ergochromes and belong to a class of mycotoxins initially isolated as major ergot pigments from the fungi Claviceps purpurea that grows parasitically on rye grasses. From early times and particularly in medieval Europe the consumption of grains containing ergot has repeatedly lead to mass poisonings known as ergotism which was caused by toxic ergot alkaloids and mycotoxins such as the ergochromes, due to contamination of flour by C. purpurea. A cluster of genes responsible for the synthesis of secalonic acids in C. purpurea has been identified. Secalonic acid D the enantiomer of secalonic acid A is a major environmental toxin, isolated from the fungus Penicillium oxalicum, and is a major microbial contaminant of freshly-harvested corn which causes toxicity through contamination of foodstuffs.
The substituted benzofurans are a class of chemical compounds based on the heterocyclyc and polycyclic compound benzofuran. Many medicines use the benzofuran core as a scaffold, but most commonly the term is used to refer to the simpler compounds in this class which include numerous psychoactive drugs, including stimulants, psychedelics and empathogens. In general, these compounds have a benzofuran core to which a 2-aminoethyl group is attached, and combined with a range of other substituents. Some psychoactive derivatives from this family have been sold under the name Benzofury.
Christopher Joseph Schofield is the Head of Organic Chemistry at the University of Oxford and a Fellow of the Royal Society. Chris Schofield is a professor of organic chemistry at the University of Oxford, Department of Chemistry and a Fellow of Hertford College. Prof Schofield studied functional, structural and mechanistic understanding of enzymes that employ oxygen and 2-oxoglutarate as a co-substrate. His work has opened up new possibilities in antibiotic research, oxygen sensing, and gene regulation.
Silvestrol is a natural product from the flavagline family, with a cyclopenta[b]benzofuran core structure and an unusual dioxane ether side chain, which is found in the bark of trees from the genus Aglaia, especially Aglaia silvestris and Aglaia foveolata.