19088-73-4

Usage

Uses

Used in Fluorogenic Substrates:
3-Cyano-7-hydroxycoumarin is used as a fluorophore for preparing fluorogenic substrates, which are essential tools in biochemistry and molecular biology. Its blue-fluorescent properties allow for the detection and quantification of specific enzymatic activities, making it a valuable component in the development of assays and research tools.
Used as a Reference Standard:
3-Cyano-7-hydroxycoumarin serves as a blue-fluorescent probe used as a reference standard in various analytical techniques. Its consistent fluorescence properties make it an ideal candidate for calibrating instruments and ensuring the accuracy of measurements in scientific research and quality control processes.
Used as a Calibration Standard:
In addition to its role as a reference standard, 3-Cyanoumbelliferone, a derivative of 3-Cyano-7-hydroxycoumarin, is also used as a calibration standard. This further highlights the versatility and importance of 3-Cyano-7-hydroxycoumarin in the field of analytical chemistry and related industries.

InChI:InChI=1/C10H5NO3/c11-5-7-3-6-1-2-8(12)4-9(6)14-10(7)13/h1-4,12H

Upstream product

• 105-56-6 ethyl 2-cyanoacetate 
• 95-01-2 2,4-Dihydroxybenzaldehyde 
• 109-77-3 malononitrile 
• 330996-72-0 7-hydroxy-2-imino-2H-chromene-3-carbonitrile 
• 1334740-01-0 C₁₅H₁₁NO₅ 
• 277309-36-1 7-Ethyloxymethyloxy-3-cyanocoumarin 
• 117620-77-6 3-Cyano-7-ethoxycoumarin 

Downstream Products

• 779-27-1 7-hydroxy-2-oxo-2H-chromene-3-carboxylic acid 
• 1032-98-0 3-(benzothiazol-2-yl)coumarin 

Relevant academic research and scientific papers

A Minimalistic Coumarin Turn-On Probe for Selective Recognition of Parallel G-Quadruplex DNA Structures

G-quadruplex (G4) DNA structures are widespread in the human genome and are implicated in biologically important processes such as telomere maintenance, gene regulation, and DNA replication. Guanine-rich sequences with potential to form G4 structures are prevalent in the promoter regions of oncogenes, and G4 sites are now considered as attractive targets for anticancer therapies. However, there are very few reports of small "druglike"optical G4 reporters that are easily accessible through one-step synthesis and that are capable of discriminating between different G4 topologies. Here, we present a small water-soluble light-up fluorescent probe that features a minimalistic amidinocoumarin-based molecular scaffold that selectively targets parallel G4 structures over antiparallel and non-G4 structures. We showed that this biocompatible ligand is able to selectively stabilize the G4 template resulting in slower DNA synthesis. By tracking individual DNA molecules, we demonstrated that the G4-stabilizing ligand perturbs DNA replication in cancer cells, resulting in decreased cell viability. Moreover, the fast-cellular entry of the probe enabled detection of nucleolar G4 structures in living cells. Finally, insights gained from the structure-activity relationships of the probe suggest the basis for the recognition of parallel G4s, opening up new avenues for the design of new biocompatible G4-specific small molecules for G4-driven theranostic applications.

A simple coumarin-based fluorescent probe for specific detection of cysteine over homocysteine and glutathione

In this work, we designed and synthesized 3-cyano-2-oxo-2H-chromen-7-yl acrylate as a simple and effective probe 1, which is capable of detecting cysteine (Cys) over other biothiols, such as homocysteine and glutathione. Remarkably, with the addition of cysteine, the 125-fold increase in fluorescence intensity of probe 1 was observed at 450?nm with excitation at 413?nm and 5?min incubation time. Furthermore, it is more important that probe 1 possesses the detection limit of 80?nM, and there is good linear relationship between fluorescence intensity and concentration of Cys from 0 to 100?μM. Thus, these made a powerful safeguard for the detection of Cys in the biological system. Simultaneously, probe 1 showed low toxicity and could be used in living cell imaging.

Pharmacokinetic evaluation of the anticancer prodrug simmitecan in different experimental animals

Aim: To investigate the pharmacokinetics and disposition of simmitecan (L-P) that was a water-soluble ester prodrug of chimmitecan (L-2-Z) with potent anti-tumor activities in different experimental animals, and to assess its drug-drug interaction potential. Methods: SD rats were injected with a single iv bolus doses of L-P (3.75, 7.5 and 15 mg/kg). The pharmacokinetics, tissue distribution, excretion and metabolism of L-P and its active metabolite L-2-Z were studied through quantitative measurements and metabolite profiling with LC/MS. The binding of L-P and L-2-Z to rat plasma proteins was examined using an ultrafiltration method. Systemic exposures of beagle dogs to L-P as well as drug distribution in tumors of the nude mice xenograft model of human hepatic cancer SMMC-7721 cells were also examined. The metabolism of L-P by liver mcirosomal carboxylesterase in vitro was investigated in different species. The effects of L-P and L-2-Z on cytochrome P450 enzymes were examined using commercial screening kits. Results: The in vivo biotransformation of L-P to L-2-Z showed a significant species difference, with a mean elimination half-life t1/2 of approximately 1.4 h in rats and 1.9 h in dogs. The systemic exposure levels of L-P and L-2-Z were increased in a dose-dependent manner. In rats, approximately 66% of L-P and 79% of L-2-Z were bound to plasma proteins. In rats and the nude mice bearing human hepatic cancers, most organ tissues had significantly higher concentrations of L-P than the corresponding plasma levels. In the tumor tissues, the L-P levels were comparable to those of plasma, whereas the L-2-Z levels were lower than the L-P levels. In rats, L-P was eliminated mainly via biliary excretion, but metabolism played an important role in elimination of the intact L-P. Finally, L-P and L-2-Z exerted moderate inhibition on the activity of CYP3A4 in vitro. Conclusion: L-P and L-2-Z have relatively short elimination half-lives and L-P is mainly eliminated via biliary excretion. The species difference in the conversion of L-P to L-2-Z and potential drug-drug interactions due to inhibition of CYP3A4 should be considered in further studies.

NEW LIQUID CRYSTALLINE MATERIAL EXHIBITING A REENTRANT NEMATIC PHASE.

The thermal properties of a homologous series of 3-cyano-7-(4 prime -(4 double prime -alkoxybenzoyloxy)benzoyloxy) coumarins have been examined. All homologs (the ethoxy to nonyloxy homologs) form high stability of the nematic phase. The heptyloxy homolog shows a reentrant behavior of the type, C-N-S//A-N-I.

Synthesis, characterization, molecular docking and DNA binding studies of Cu(II), Ni(II), Zn(II) and Mn(II) complexes

The azo dye ligand of Cyano-6-(p-tolyl)azo-7-hydroxy coumarine (HL) was synthesized by coupling of 3-Cyano-7-hydroxy coumarine with p-toluidine. The ligand (HL) was formed novel complexes (1–4) with the formulae [Cu(L)Cl(OH2)]2H2O, [Ni(L)Cl(OH2)3], [Zn(L)Cl(OH2)]H2O and [Mn(L)Cl(OH2)3]2H2O, respectively. HL and its complexes were characterized by elemental analyses, IR, 1H NMR, MS and UV–Visible spectra as well as magnetic and thermal measurements. The molar conductance measurements proved that all the complexes are non-electrolytes. Also, the important fragments in the ligand and Ni(II) complex were done using mass spectra and the main peaks were corresponding to the molecular weights of them. IR spectra shows that the ligand (HL) act as monobasic bidentate coordinated via nitrogen atom of the azo group ([sbnd]N[dbnd]N[sbnd]) and oxygen atom of the deprotonated phenolic OH group. The Thermal decomposition of the complexes revealed the outer and inner water molecules as well as the end product which in most cases is metal oxide. The thermodynamic parameter of the ligand (HL) and its metal complexes are calculated using Coats-Redfern and Horowitz Metzger methods. The molecular and electronic structures of the investigated compounds were also studied using quantum chemical calculations. The bonding parameter of the complexes have been calculated. Molecular docking was used to predict the binding between azo compounds with the receptor of breast cancer 3hb5-oxidoreductase and prostate cancer mutant 2q7k–Hormone. The calf thymus DNA binding activity of the ligand (HL) and its metal complexes were studied by absorption spectra. The cytotoxic activity of ligand (HL) and its metal complexes was tested against human cancer MCF-7 (breast cancer).

THERMAL AND DIELECTRIC PROPERTIES OF LIQUID CRYSTALS WITH A COUMARIN SKELETON.

In order to examine the liquid crystalline properties of coumarin, 3-X- and 7-Y-substituted coumarins where X equals cyano and n-alkoxycarbonyl, and Y equals 4-n-alkyl- and 4-n-alkoxybenzoyl, 4-alkoxycinnamoyloxy, 4 prime -alkyl- and 4 prime -alkoxy-4-biphenylylcarbonyloxy, and 4-(4-alkoxybenzoyloxy)benzoyloxy groups have been prepared. The compounds with X equals alkoxycarbonyl groups tend to exhibit strong smectic properties, and compounds with X equals cyano exhibit stable nematic phases, whereas the coumarin core seems to facilitate a lateral separation of molecules in the mesophase due to its large molecular breadth. The thermal properties are discussed in terms of the polarity and polarizability of coumarin, and the molecular structure.

Novel coumarin-based sensitive and selective fluorescent probes for biothiols in aqueous solution and in living cells

Two novel coumarin-derived fluorescent probes were designed and synthesized for the quantitative determination of biothiols, such as cysteine (Cys), glutathione (GSH) and homocysteine (Hcy). Both probes selectively and sensitively detected biothiols in vi

Simultaneous measurement of CYP1A2 activity, regioselectivity, and coupling: Implications for environmental sensitivity of enzyme-substrate binding

The cytochrome P450 (CYP) reaction mechanism often yields a broad array of coupled and uncoupled products from a single substrate. While it is well known that reaction conditions can drastically affect the rate of P450 catalysis, their effects on regioselectivity and coupling are not well characterized. To investigate such effects, the CYP1A2 oxidation of 7-ethoxymethoxy-3- cyanocoumarin (EOMCC) was examined as a function of buffer type, buffer concentration, pH, and temperature. A high-throughput, optical method was developed to simultaneously measure the rate of substrate depletion, NADPH depletion, and generation of the O-dealkylated product. Increasing the phosphate buffer concentration and temperature increased both the NADPH and EOMCC depletion rates by 6-fold, whereas coupling was constant at 7.9% and the regioselectivity of O-dealkylation to other coupled pathways was constant at 21.7%. Varying the buffer type and pH increased NADPH depletion by 2.5-fold and EOMCC depletion by 3.5-fold; however, neither coupling nor regioselectivity was constant, with variations of 14.4% and 21.6%, respectively. Because the enzyme-substrate binding interaction is a primary determinant of both coupling and regioselectivity, it is reasonable to conclude that ionic strength, as varied by the buffer concentration, and temperature alter the rate without affecting binding while buffer type and pH alter both.

Antagonistic activity of hydroxycoumarin-based antioxidants as possible singlet oxygen precursor photosensitizers

Coumarins are phenolic-type compounds with efficient antioxidant activity due to their ability to scavenge reactive oxygen species. Nevertheless, their ability to behave as photosensitizers capable of generating reactive oxygen species, such as singlet oxygen, has been less studied. In this work, the photosensitizing ability of seven hydroxycoumarins was evaluated through the photooxidation of ergosterol by quantifying the conversion of ergosterol into ergosterol peroxide. In our experimental conditions, we found that almost every tested antioxidant coumarin promotes the peroxidation of ergosterol. The results suggest that the hydroxycoumarins exhibit potential photosensitizing activity by promoting singlet oxygen generation by a Type II photochemical mechanism. Density functional theory (DFT) calculations were also performed to obtain further insight into the chemical reactivity of tested compounds; the observed tendency in the group of antioxidant coumarins to promote the reaction was their hardness due to the principle of maximum hardness. To evaluate our conclusion, we performed the reaction using a highly polarizable coumarin as a photosensitizer, which resulted in an increased photosensitizing capacity supported with DFT calculations, which reinforces our analysis. Finally, we found that hydroxycoumarins can be potentially pro-oxidants since some of them can act as photosensitizers and generate singlet oxygen in the presence of UV–Vis light, a characteristic that must be considered when these compounds are used as antioxidants.

Functional and structural characterisation of common cytochrome P450 2D6 allelic variants—roles of Pro34 and Thr107 in catalysis and inhibition

One major source of inter-individual variability in drug pharmacokinetics is genetic polymorphism of the cytochrome P450 (CYP) genes. This study aimed to elucidate the enzyme kinetic and molecular basis for altered activity in three major alleles of CYP2D6, namely CYP2D6*2, CYP2D6*10 and CYP2D6*17. The E. coli-expressed allelic variants were examined using substrate (venlafaxine and 3-cyano-7-ethoxycoumarin[CEC]) and inhibitor (quinidine, fluoxetine, paroxetine, terbinafine) probes in enzyme assays as well as molecular docking. The kinetics data indicated that R296C and S486T mutations in CYP2D6*2 have caused enhanced ligand binding (enhanced intrinsic clearance for venlafaxine and reduced IC50 for quinidine, paroxetine and terbinafine), suggesting morphological changes within the active site cavity that favoured ligand docking and binding. Mutations in CYP2D6*10 and CYP2D6*17 tended to cause deleterious effect on catalysis, with reduced clearance for venlafaxine and CEC. Molecular docking indicated that P34S and T107I, the unique mutations in the alleles, have negatively impacted activity by affecting ligand access and binding due to alteration of the substrate access channel and active site morphology. IC50 values however were quite variable for quinidine, fluoxetine and terbinafine, and a general decrease in IC50 was observed for paroxetine, suggesting ligand-specific altered susceptibility to inhibition in the alleles. This study indicates that CYP2D6 allele selectivity for ligands was not solely governed by changes in the active site architecture induced by the mutations, but that the intrinsic properties of the substrates and inhibitors also played vital role.