Naturally Occurring Plant Coumarins
TL;DR: 7-hydroxycoumarin [umbelliferone, (2)], one of the most widely distributed coumarins, is often regarded as the parent, in a structural sense and also biogenetically, of a large number of the structurally more complex coumarin.
Abstract: Over the past 150 years, since Vogel in 1820 isolated the parent oxygen heterocycle, coumarin (1) from Coumarouna odorata = Dipteryx odorata (1), coumarins have been recognized as widely distributed plant products. The vast majority carry an oxygen substituent at C-7; consequently 7-hydroxycoumarin [umbelliferone, (2)], one of the most widely distributed coumarins, is often regarded as the parent, in a structural sense and also biogenetically, of a large number of the structurally more complex coumarins. A number of review articles on natural plant coumarins have appeared (154, 302, 344, 420, 525, 541, 548) since the last in this series (153), the most comprehensive, albeit dealing solely with coumarins of the Umbelliferae, being that of Nielsen in 1970 (419).
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TL;DR: An overview of the most recent synthetic pathways leading to mono- and polyfunctionalized coumarins will be presented, along with the main biological pathways of their biosynthesis and metabolic transformations.
Abstract: Many naturally occurring substances, traditionally used in popular medicines around the world, contain the coumarin moiety. Coumarin represents a privileged scaffold for medicinal chemists, because of its peculiar physicochemical features, and the versatile and easy synthetic transformation into a large variety of functionalized coumarins. As a consequence, a huge number of coumarin derivatives have been designed, synthesized, and tested to address many pharmacological targets in a selective way, e.g., selective enzyme inhibitors, and more recently, a number of selected targets (multitarget ligands) involved in multifactorial diseases, such as Alzheimer’s and Parkinson’s diseases. In this review an overview of the most recent synthetic pathways leading to mono- and polyfunctionalized coumarins will be presented, along with the main biological pathways of their biosynthesis and metabolic transformations. The many existing and recent reviews in the field prompted us to make some drastic selections, and therefore, the review is focused on monoamine oxidase, cholinesterase, and aromatase inhibitors, and on multitarget coumarins acting on selected targets of neurodegenerative diseases.
349 citations
30 Sep 2015
TL;DR: There may be as many as 4,000 different phytochemicals having potential activity against several diseases such as cancer and metabolic or degenerative diseases, but not all are established as essential nutrients.
Abstract: Phytochemicals are chemical compounds that occur naturally in the plant kingdom. Some are responsible for the organoleptic properties of the natural sources in which they are present. The term is generally used to refer to those chemicals that may have biological significance, for example carotenoids, flavonoids, coumarins, or chromones, but not all are established as essential nutrients. There may be as many as 4,000 different phytochemicals having potential activity against several diseases such as cancer and metabolic or degenerative diseases.
128 citations
Cites background from "Naturally Occurring Plant Coumarins..."
...Coumarinic compounds are a class of lactones structurally constructed by a benzene ring fused to α-pyrone ring, and essentially possess - conjugated system with rich electron and good charge-transport properties [4, 5]....
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TL;DR: A combination of these structural features, two methoxy functions and at least one additional phenolic group as reflected by the highly oxygenated coumarins, identify promising candidates with antibacterial broad-spectrum activity.
Abstract: The antibacterial activity of a series of simple coumarins was evaluated against 8 microorganisms, including three Gram-positive (Staphylococcus aureus, beta-hemolytic Streptococcus and Streptococcus pneumoniae) and five Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis and Haemophilus influenzae), using the microdilution broth method. The coumarins tested showed broad diversity regarding growth inhibitory activity with minimum inhibitory concentrations ranging from 0.9 to > 12.4 microM. This study, presenting the first systematic analysis of structure-activity relationships among this group of coumarins, revealed some interesting structural requirements. While coumarins with a methoxy function at C-7 and, if present, an OH group at either the C-6 or C-8 position are invariably effective against the spectrum of tested standard bacteria (Gram-negative microorganisms including the Gram-positive bacterium Staphylococcus aureus), the presence of an aromatic dimethoxy arrangement is apparently favourable against those microorganisms which require special growth factors (beta-hemolytic Streptococcus, Streptococcus pneumoniae and Haemophilus influenzae). A combination of these structural features, two methoxy functions and at least one additional phenolic group as reflected by the highly oxygenated coumarins, identify promising candidates with antibacterial broad-spectrum activity.
121 citations
TL;DR: Apioideae were investigated by comparative sequencing of the two internal transcribed spacers of the 18S–26S nuclear ribosomal DNA repeat, clarified the relationships of several genera whose phylogenetic placements have heretofore been problematic.
Abstract: Evolutionary relationships among 116 representatives (80 genera) ofApiaceae (Umbelliferae) subfam.Apioideae were investigated by comparative sequencing of the two internal transcribed spacers of the 18S–26S nuclear ribosomal DNA repeat. The resultant phylogenies, inferred using maximum parsimony and neighbor-joining methods, clarified the relationships of several genera whose phylogenetic placements have heretofore been problematic. Comparisons between the phylogenies inferred and the distribution of several phytochemical (coumarins, flavonoids, and phenylpropenes) and morphological (stomates, pollen, and cotyledonary shape) characters were also made, revealing that many of these characters (like those morphological and anatomical characters of the fruit) are highly homoplastic. It is not surprising then that systems of classification ofApioideae based on these characters, particularly with regard to tribal and subtribal designations and relationships, are unsatisfactory. The results of recent serological investigations of the subfamily support several relationships proposed herein using molecular data.
120 citations
TL;DR: The studies and development of new compounds for AD treatment are discussed, which objective is to increase the concentration of ACh in the synaptic cleft by the inhibition of cholinesterases.
111 citations
References
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TL;DR: Calanolide A was active not only against the AZT-resistant G-9106 strain of HIV-1 but also against the pyridinone-resistant A17 strain, which was of particular interest since the A17 virus is highly resistant to previously known HIV- 1 specific, non-nucleoside RT inhibitors.
Abstract: Eight new coumarin compounds (1-8) were isolated by anti-HIV bioassay-guided fractionation of an extract of Calophyllum lanigerum. The structures of calanolide A (1), 12-acetoxycalanolide A (2), 12-methoxycalanolide A (3), calanolide B (4), 12-methoxycalanolide B (5), calanolide C (6) and related derivatives 7 and 8 were solved by extensive spectroscopic analyses, particularly HMQC, HMBC, and difference NOE NMR experiments. The absolute stereochemistry of calanolide A (1) and calanolide B (4) was established by a modified Mosher's method. Calanolides A (1) and B (4) were completely protective against HIV-1 replication and cytopathicity (EC50 values of 0.1 microM and 0.4 microM, respectively), but were inactive against HIV-2. Some of the related compounds also showed evidence of anti-HIV-1 activity. Studies with purified bacterial recombinant reverse transcriptases (RT) revealed that the calanolides are HIV-1 specific RT inhibitors. Moreover, calanolide A was active not only against the AZT-resistant G-9106 strain of HIV-1 but also against the pyridinone-resistant A17 strain. This was of particular interest since the A17 virus is highly resistant to previously known HIV-1 specific, non-nucleoside RT inhibitors (e.g., TIBO; BI-RG-587; L693,593) which comprise a structurally diverse but apparently common pharmacologic class. The calanolides represent a substantial departure from the known class and therefore provide a novel new anti-HIV chemotype for drug development.
540 citations
250 citations