Design, synthesis and evaluation of structurally diverse ortho-acylphenol-diindolylmethane hybrids as anticancer agents

A highly efficient synthesis of structurally diverse ortho-acylphenol–diindolylmethane hybrids 3 using carboxylic acid-activated chromones as versatile synthetic building blocks is reported here for the first time, through 1,4-nucleophilic addition and followed by a decarboxylation and pyrone ring opening reaction process.

Synthesis and Reactivity of Electron-Deficient 3-Vinylchromones

The reported methods and data for the synthesis and reactivity of electron-deficient 3-vinylchromones containing electron-withdrawing­ groups at the exo-cyclic double bond are summarized and systematized for the first time. The main methods for obtaining these compounds are Knoevenagel condensation, Wittig reaction, and palladium-catalyzed cross-couplings. The most important chemical properties are transformations under the action of mono- and dinucleophiles, ambiphilic cyclizations, and cycloaddition reactions. The cross-conjugated and polyelectrophilic dienone system in 3-vinylchromones provides their high reactivity and makes these compounds valuable building blocks for the preparation of more complex heterocyclic systems. Chemical transformations of 3-vinylchromones usually begin with an attack of the C-2 atom and are accompanied by the opening of the pyrone ring followed by recyclization, in which the carbonyl group of chromone, an exo-double bond or a substituent on it can take part. The mechanisms of the reactions are discussed, the conditions for their implementation are described, and the yields of the resulting products are given. This review focuses on an analysis and generalization of the knowledge that has accumulated on the chemistry of electron-deficient 3-vinylchromones, mostly over the past 15 years.1 Introduction2 Synthesis of 3-Vinylchromones3 Reactions with Mononucleophiles4 Reactions with Dinucleophiles5 Ambiphilic Cyclization6 Cycloaddition Reactions7 Other Reactions8 Conclusion

Biological Activities Related to Plant Protection and Environmental Effects of Coumarin Derivatives: QSAR and Molecular Docking Studies

The aim was to study the inhibitory effects of coumarin derivatives on the plant pathogenic fungi, as well as beneficial bacteria and nematodes. The antifungal assay was performed on four cultures of phytopathogenic fungi by measuring the radial growth of the fungal colonies. Antibacterial activity was determined by the broth microdilution method performed on two beneficial soil organisms. Nematicidal activity was tested on two entomopathogenic nematodes. The quantitative structure-activity relationship (QSAR) model was generated by genetic algorithm, and toxicity was estimated by T.E.S.T. software. The mode of inhibition of enzymes related to the antifungal activity is elucidated by molecular docking. Coumarin derivatives were most effective against Macrophomina phaseolina and Sclerotinia sclerotiorum, but were not harmful against beneficial nematodes and bacteria. A predictive QSAR model was obtained for the activity against M. phaseolina (R2tr = 0.78; R2ext= 0.67; Q2loo = 0.67). A QSAR study showed that multiple electron-withdrawal groups, especially at position C-3, enhanced activities against M. phaseolina, while the hydrophobic benzoyl group at the pyrone ring, and –Br, –OH, -OCH3, at the benzene ring, may increase inhibition of S. sclerotiourum. Tested compounds possibly act inhibitory against plant wall-degrading enzymes, proteinase K. Coumarin derivatives are the potentially active ingredient of environmentally friendly plant-protection products.

Facile Synthesis of Polysubstituted 2-Pyrones via TfOH-Mediated Ring Expansion of 2-Acylcyclopropane-1-Carboxylates

A facile route to polysubstituted 2-pyrones from readily available 2-acylcyclopropane-1-aryl-1-carboxylates mediated by TfOH is reported. The strongly donating 1-aryl group is important for directing the C-C bond cleavage of the donor-acceptor cyclopropane ring, which then leads to the formation of the 2-pyrone ring through lactonization.

Synthetic Routes to Coumarin(Benzopyrone)-Fused Five-Membered Aromatic Heterocycles Built on the α-Pyrone Moiety. Part II: Five-Membered Aromatic Rings with Multi Heteroatoms

Coumarins are natural heterocycles that widely contribute to the design of various biologically active compounds. Fusing different aromatic heterocycles with coumarin at its 3,4-position is one of the interesting approaches to generating novel molecules with various biological activities. During our continuing interest in assembling information about fused five-membered aromatic heterocycles, and after having presented mono-hetero-atomic five-membered aromatic heterocycles in Part I. The current review Part II is intended to present an overview of the different synthetic routes to coumarin (benzopyrone)-fused five-membered aromatic heterocycles with multi-heteroatoms built on the pyrone ring, covering the literature from 1945 to 2021.

A Comparison Study on Fluorescence Properties of Formononetin and Ononin

In this work, reasons for the spectral difference between two isoflavones, Formononetin (F) and ononin (FG), are explained in the viewpoint of molecular structure through a comparison study of the fluorescence features of the two. The fluorescence enhancement of FG in hot alkaline condition is reported for the first time. For F, there was almost no fluorescence under acidic conditions, but when pH>5, its fluorescence began to increase with increasing pH due to the proton ionization of 7-OH. In the range of pH 9.3-12.0, the anion form of F produced a fairly strong and stable fluorescence with maximum excitation wavelength (λex) of 334 nm and emission wavelength (λem) of 464 nm, its fluorescence quantum yield (Yf) was measured to be 0.042. And for FG, its aqueous solution fluoresced weakly in a wide pH range until it was placed under hot alkaline conditions, which was presumed to the cleavage reaction of the γ-pyrone ring in FG by observing a significant fluorescence at λex / λem =288 / 388nm, and Yf was determined to be 0.020. The fluorescence sensitization methods of F and FG both exhibit low limits of detection (2.60 ng·mL-1, 9.30 ng·mL-1) and wide linear ranges (0.0117-1.86 μg·mL-1, 0.0146-2.92μg·mL-1). Although the structural relationship between F and FG is glycoside and aglycone, FG cannot be translated to F by glucoside hydrolysis under hot alkaline condition, the fluorescence enhancement mechanisms of the two are essentially different. The fluorescence difference between the two under different experimental conditions lays the foundation for future fluorescence quantitative analysis.

The First Step of Biodegradation of 7-Hydroxycoumarin in Pseudomonas mandelii 7HK4 Depends on an Alcohol Dehydrogenase-Type Enzyme

Coumarins are well known secondary metabolites widely found in various plants. However, the degradation of these compounds in the environment has not been studied in detail, and, especially, the initial stages of the catabolic pathways of coumarins are not fully understood. A soil isolate Pseudomonas mandelii 7HK4 is able to degrade 7-hydroxycoumarin (umbelliferone) via the formation of 3-(2,4-dihydroxyphenyl)propionic acid, but the enzymes catalyzing the α-pyrone ring transformations have not been characterized. To elucidate an upper pathway of the catabolism of 7-hydroxycoumarin, 7-hydroxycoumarin-inducible genes hcdD, hcdE, hcdF, and hcdG were identified by RT-qPCR analysis. The DNA fragment encoding a putative alcohol dehydrogenase HcdE was cloned, and the recombinant protein catalyzed the NADPH-dependent reduction of 7-hydroxycoumarin both in vivo and in vitro. The reaction product was isolated and characterized as a 7-hydroxy-3,4-dihydrocoumarin based on HPLC-MS and NMR analyses. In addition, the HcdE was active towards 6,7-dihydroxycoumarin, 6-hydroxycoumarin, 6-methylcoumarin and coumarin. Thus, in contrast to the well-known fact that the ene-reductases usually participate in the reduction of the double bond, an alcohol dehydrogenase catalyzing such reaction has been identified, and, for P. mandelii 7HK4, 7-hydroxycoumarin degradation via a 7-hydroxy-3,4-dihydrocoumarin pathway has been proposed.

Psoralen: A Biologically Important Coumarin with Emerging Applications

Coumarin belongs to a class of lactones that are fundamentally comprised of a benzene ring fused to an α-pyrone ring; these lactones are known as benzopyrones. Similarly, coumarin has a conjugated electron-rich framework and good charge-transport properties. Plants produce coumarin as a chemical response to protect themselves from predation. Coumarins are used in different products, such as cosmetics, additives, perfumes, aroma enhancers in various tobaccos and some alcoholic drinks, and they play a relevant role in natural products and in organic and medicinal chemistry. In addition, as candidate drugs, many coumarin compounds have strong pharmacological activity, low toxicity, high bioavailability and better curative effects and have been used to treat various types of diseases. Various endeavors were made to create coumarin-based anticoagulant, antimicrobial, antioxidant, anticancer, antidiabetic, antineurodegenerative, analgesic and anti-inflammatory agents. A class of chemical compounds called furocoumarins has phototoxic properties and is naturally synthesized via the fusion of coumarin to a furan ring in different plant species. Psoralens belong to the furocoumarin class and occur naturally in various plants, e.g., lemons, limes, and parsnips. Angelicin is an isomer of psoralens, and most furocoumarins, e.g., xanthotoxin, bergapten, and nodekenetin, are derivatives of psoralens or angelicin. The present work demonstrated that psoralen molecules exhibit anti-tumoral activity against breast cancer and influence different intracellular signals to maintain the high survival of breast cancer cells. Psoralens perform different functions, e.g., antagonize metabolic pathways, protease enzymes, and cell cycle progression and even interfere in the crosslinking between receptors and growth factor mitogenic signaling.

Antimicrobial Meroterpenoids and Erythritol Derivatives Isolated from the Marine-Algal-Derived Endophytic Fungus Penicillium chrysogenum XNM-12

One new meroterpenoid-type alkaloid, oxalicine C (1), and two new erythritol derivatives, penicierythritols A (6) and B (7), together with four known meroterpenoids (2–5), were isolated from the marine algal-derived endophytic fungus Penicillium chrysogenum XNM-12. Their planar structures were determined by means of spectroscopic analyses, including UV, 1D and 2D NMR, and HRESIMS spectra. Their stereochemical configurations were established by comparing the experimental and calculated electronic circular dichroism (ECD) spectra for compound 1, as well as by comparison of the optical rotations with literature data for compounds 6 and 7. Notably, oxalicine C (1) represents the first example of an oxalicine alkaloid with a cleaved α-pyrone ring, whereas penicierythritols A (6) and B (7) are the first reported from the Penicillium species. The antimicrobial activities of compounds 1–7 were evaluated. Compounds 1 and 6 exhibited moderate antibacterial effects against the plant pathogen Ralstonia solanacearum with minimum inhibitory concentration (MIC) values of 8 and 4 μg/mL, respectively. Compound 6 also possesses moderate antifungal properties against the plant pathogen Alternaria alternata with a MIC value of 8 μg/mL.

A Review: Synthesis and Medicinal Importance of Coumarins and their Analogues (Part II)

Coumarins are a set of polyphenolic compounds isolated from plant product tonka bean, coumarou in 1820. They belong to the family of benzopyrones, which includes benzene ring joined with the aid of a pyrone ring. Coumarins have attracted great attention of medicinal chemists and pharmacologists in recent years as they been confirmed to bear diverse pharmacological activities like antiinflammatory and analgesic, anti oxidant, anticancer, etc. This review highlights the method of preparation, chemical reactivity, and organic properties such as anti-inflammatory, anticoagulant, antioxidant, anticancer and analgesic activities, of coumarins and their analogues.