Synthesis Of New Coumarin Derivatives Research Articles

Synthesis and comprehensive spectroscopic (X-ray, NMR, FTIR, UV–Vis), quantum chemical and molecular docking investigation of 3-acetyl-4‑hydroxy‑2-oxo-2H-chromen-7-yl acetate

In the present study, the structural, spectroscopic (FT-IR, NMR, and UV–Vis) and electronic properties of newly synthesized 3-acetyl-4‑hydroxy‑2-oxo-2H-chromen-7-yl acetate (3AcHyC) were determined by experimental and theoretical methods. The structural parameters (bond lengths and angles) were calculated using the B3LYP-D3BJ/6–311++G(d,p) theoretical model and compared with the experimentally determined crystal structure of the investigated compound. Hirshfeld surfaces and fingerprint plots analysis were used to find and analyze the percentage of intermolecular interactions in the crystal structure of the investigated compound. The calculated FT-IR frequencies were determined from the same theoretical model and matched with experimental data. The NMR chemical shifts (1H and 13C) were recorded in the CDCl3 solution and compared with theoretically determined spectra. The UV–Vis absorption spectrum was analyzed and compared with the spectrum calculated by Time-Dependent Density Functional Theory (TD-DFT). The obtained and compared spectroscopic data demonstrated that applied level theory reproduces well the experimental results. Furthermore, to examine the electronic structure of the studied molecule, the Natural Bond Orbitals (NBOs), the Quantum Theory of Atoms in Molecules (QTAIM), Non-linear Optical parameter (NLO), and Mapped Molecular Electrostatic Potential (MEP) surface analyses were also performed with the same level of theory. Furthermore, results of in silico molecular docking calculations, indicate the stability as well as favorable binding interactions between the investigated compound and the Tyrosyl DNA-Phosphodiesterase 1 (TDP1) active site. Also, the results indicate that the investigated compound is a favorable precursor in the synthesis of new coumarin derivatives with potentially significant biological and pharmacological properties.

Synthesis, structure, cytotoxic and antioxidant properties of 6-ethoxy-4-methylcoumarin

Coumarins have a wide usage area in medicinal applications. It is known that the design and synthesis of new coumarin derivatives are performed to prepare new drugs in many laboratories. The aim of the study was to synthesize 6-ethoxy-4-methylcoumarin and detect its chemical and biological properties for the first time. 6-ethoxy-4-methylcoumarin was synthesized using Pechmann method. Atomic orbital (GIAO) 1H and 13C NMR chemical shift values in the ground state were calculated and Density Functional Method (DFT) was applied with the 6–311++G (d, p) basis set to determine chemical properties. 6-ethoxy-4-methylcoumarin was applied to cultured blood samples at various concentrations (10–400 mg/L) for determining biological activity. 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays were used to evaluate cytotoxic effect. In addition, total antioxidant capacity (TAC) and total oxidative status (TOS) were examined to determine antioxidant properties. The results showed that theoretical vibrational frequencies and chemical shift values were close to experimental values. Moreover, 6-ethoxy-4-methylcoumarin showed a slight cytotoxic effect at dose of 200 mg/L and exhibited an antioxidant activity at 25 mg/L concentration without changing oxidative status at all of doses.

An Efficient One‐Pot Synthesis of New Coumarin Derivatives as Potent Anticancer Agents under Microwave Irradiation

An efficient and rapid synthesis of coumarin derivatives was accomplished via reactions of 3‐(3‐(4‐methoxyphenyl)acryloyl)‐2H‐chromen‐2‐one (3) with different carbon nucleophiles such as ethyl acetoacetate, ethyl cyanoacetate, malononitrile, and ethyl benzoylacetate via conventional heating and microwave irradiation conditions and were used as source of pyran and pyridine derivatives bearing coumarin moiety 4–11. Compound 9a was condensed with different carbon electrophiles triethylorthoformate, phenylisothiocyanate, carbon disulfide, benzoylchloride, and acetylchloride that afforded the corresponding chromen derivatives 12–16. All the newly synthesized compounds were characterized by elemental and spectroscopic evidences. All of synthesized compounds were tested for in vitro cytotoxicity. The preliminary screening results showed that most of the compounds had moderate cytotoxic activity against HCT‐116 and MCF‐7 cell lines. Nevertheless, compound 10 exhibited potent activity against the two cell lines, which was comparable with the standard drug 5‐fluorouracil.

Microwave-assisted synthesis of some new coumarin derivatives including 1,2,4-triazol-3-one and investigation of their biological activities

By using the microwave technology, a new protocol has been developed for the synthesis of new coumarin derivatives including 1,2,4-triazol-3-one skeleton. This protocol proves to be efficient and environmentally friendly in terms of easy work-up and good yields. All newly synthesized compounds were screened for their antimicrobial activity and lipase inhibition. Most of the compounds were found to be effective on Escherichia coli. N'-{[4-Amino-3-(2-bromobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetyl}-6-bromo-2-oxo-2Hchromene-3-carbohydrazide and N'-{[4-amino-3-(3,4-dichlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetyl}-6-bromo-2-oxo-2H-chromene-3-carbohydrazide had a good effect on lipase inhibition.

SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL COUMARIN DERIVATIVES AS ANTIOXIDANT AGENTS.

Coumarins have been isolated from plants and reported for antioxidant properties. In the present study, we report synthesis of new coumarin derivatives as prospective therapeutic agents and investigate their antioxidant properties.

Synthesis, reactions, antioxidant and anticancer evaluation of some novel coumarin derivatives using ethyl 2-(2-oxo-4-phenyl-2H-chromen-7-yloxy) acetate as a starting material

We report on the synthesis of new coumarin derivatives coupled with heterocyclic and bifunctionalized moieties at position 7. The proposed structures were confirmed by correct elemental analysis and spectral data (IR, MS, 1 H NMR and 13 C NMR). Some selected derivatives were also screened for their antioxidant and anticancer activities. The results indicated that 7-{[6-(4-nitrophenyl)-7 H -[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl]methoxy}-4-phenyl- H -chromen-2-one has the highest antioxidant and anticancer activity in tested compounds.

Synthesis of new coumarin derivatives with suspected anticoagulant activity

Objectives: To synthesize three series of new coumarin derivatives and to screen their anticoagulant activity in rabbits in order to define in more exact terms the structural features that responsible for the anticoagulant activity of coumarins. Methods: the first series was synthesized by esterification the 7-hydroxycoumarin with benzoic acid, salicylic acid and 5-amino salicylic acid to give derivatives I-III; the second series was synthesized by the formation of amide linkage between 6-aminocoumarin and benzoic acid, salicylic acid and 5-amino salicylic acid to give derivatives IV-VI while the third series was synthesized by esterification the coumarin-6-carboxylic acid with phenol, resorcinol and m-chlorophenol to give derivatives VII-IX. The anticoagulant activity of these derivatives (I-IX) was investigated in rabbits via Quick's one-stage method; the initial effect of each derivative on the prothrombine time for five rabbits before and after oral administration was measured. Results: The chemical structure of these derivatives was characterized by physical and spectroscopic techniques as FTIR, UV and 13C-NMR spectra. Depending on prothrombin time measurements, derivatives II and VIII showed a significant anticoagulant activity through increasing the prothrombine time while the other derivatives showed an insignificant anticoagulant activity. Conclusion: This study proposed that the coumarin derivatives contained an ester linkage at position 6 or 7 separated from a hydroxyl group by short carbon side chain may show anticoagulant activity.

Electrochemical synthesis of new coumarin derivatives of potential biological significance

Electrochemical synthesis of some new coumarin derivatives was carried out via the electrochemical oxidation of 1-(4-(4-hydroxyphenyl)piperazin-1-yl)ethanone (1) in the presence of 4-hydroxycoumarin and 4-hydroxy-6-methylcoumarin (2a,b). The results show that, electrogenerated p-quinone imine, participated in Michael type reaction with 2a,b and after hydrolysis reaction is converted to the corresponding coumarin derivatives. This method provides a one-pot procedure for the synthesis of new coumarin derivatives of potential biological significance.

Design, synthesis and bioassay of novel coumarins

In Iraq like most third world countries, attempts to discover new antibiotic drugs derived from coumarins moreover develop the branch of applied in organic chemistry. Novel coumarin derivatives were synthesized in a good yield through converting lacton to lactam and study the biological activity of the synthesized compounds. Coumarins were characterized by elemental analysis, FT-IR, 1H-NMR and UV/visible spectra. The novel coumarins have been tested in vitroagainst (gram positive bacteria Staphylococcus aureus and against other gram negative bacteria, such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Proteus vulgaris; in order to assess their antimicrobial properties. Moreover, charge, bond length, bond angle, twist angle, heat of formation and steric energy were calculated by using of the ChemOffice program. The study indicates that these coumarins have high activity against tested bacteria. Based on the reported results, it may be concluded that the coumarin act as synthons for synthesis of new coumarin derivatives through the replacement of oxygen atom by nitrogen atom. Key words: Biological activity, coumarins, oxoquinolin, thiourea.

The Synthesis and Antimicrobial Activity of Some 4-Hydroxycoumarin Derivatives

Due to exceptional reactivity of 4-hydroxycoumarin, the synthesis of new coumarin derivatives of dimer and tetramer type has been carried out. The synthesis was carried out from 4-hydroxycoumarin and various aromatic aldehydes. In this way, compounds of the dimer 3,3'-(benzilidene)bis (4-hydroxycoumarin) type, as well as of the tetramer 3,3',3'',3'''-(1,4-dimethylenphenyl)tetra (4-hydroxycoumarin) type were prepared. The newly synthesized derivatives contain different functional groups, and as such they could exhibit microbiological activity. Therefore, we tested the microbiological activity of these derivatives on various species of bacteria and fungi. The tested compounds have shown different activity in terms of growth inhibition of microorganisms. Newly synthesized derivatives exhibit antibacterial activities, manifested as growth inhibition on Gram-positive bacteria types (Bacillus, Staphylococcus), while the activity against Candida was much weaker. The same compound did not show any antimicrobial activity against two Gram-negative bacteria types (Escherichia coli, Pseudomonas aeruginosa). The compound 1 showed the best microbiological activity. The obtained results confirmed its good antibacterial and antimycotic activities against different microorganisms.

The 4-arylaminocoumarin derivatives log P values calculated according to Rekker's method

In the QSAR (quantitative structure-activity relationship) and QSPR (quantitative structure-property-activity relationship) study physico-chemical property, lipophilicity is used, to predict bioactivity of the newly synthesized coumarin compounds. Lipophilicity is a property of a molecule which depends on and can be changed by modifications in molecular structure. The parameter of the lipophilicity, partition coefficient (log P), is commonly used in drug designing and it is a numeric characteristic of lipophilicity of the examined substance, potential drug. The synthesis of 4-arylaminocoumarins derivatives from 4-hydroxycoumarin, has been carried out. In this work we described the fragmental method of calculation of partition coefficient according to the Rekker's method, because the best correlation between calculated and experimental values log P was determined according to the Rekker model. 4-Arylaminocoumarin has negative value of log P, but substitution with alkyl or allyl groups on the position 3 increases lipofilicity. Introduction of methyl or ethyl group into position 3 increases lipofilicity, suggesting that by increasing the chain length the values of log P become higher. The influence of allyl substituent in position three increases lipophilicity similar to methyl group. The aryl supstitent decreases lipoflicity, but a general relationship among them could not be established. The results obtained in this study enable further synthesis of new coumarin derivatives and predict their biological activity and properties.

QSAR and QSPR study of derivatives 4-arylaminocoumarin

Coumarin and its derivatives are reactive compounds, suitable for many syntheses. They are used as anticoagulants, antibacterial, animistic compounds. The interest in coumarins has increased because it was found that they reduce the HIV virus activity. The synthesis of 4-arylaminocoumarin derivatives from 4-hydroxycoumarin, has been carried out, and their antimycotic effects were tested. In the QSAR (quantitative structure-activity relationship) QSPR (quantitative structure-property-activity relationship) study we have used physicochemical properties and topological indices (Balaban index J(G), Wiener index W(G), information-theoretical index I(G), and valence connectivity index (G), to predict bioactivity of the newly synthesized coumarin compounds. By using methods of molecular modelling, the relationships between structure, properties and activity of coumarin compounds have been investigated. The best QSPR models were obtained using valence connectivity index or combination indices. According Rekker's method the best correlation of calculated values log P, has been obtained with the model based on the inhibition zone (I) 4-arylaminocoumarin derivatives expressed in mm. The results obtained in this study enable further synthesis of new coumarin derivatives and predict their biological activity and properties.