Coumarin Thiazole Research Articles

A comprehensive assessment on coumarin–thiazole composite as a versatile scaffold for the potent multifunctional bioactive agents

A comprehensive assessment on coumarin–thiazole composite as a versatile scaffold for the potent multifunctional bioactive agents

Novel chalcone-conjugated, multi-flexible end-group coumarin thiazole hybrids as potential antibacterial repressors against methicillin-resistant Staphylococcus aureus

The increasing resistance of methicillin-resistant Staphylococcus aureus (MRSA) to antibiotics has led to a growing effort to design and synthesize novel structural candidates of chalcone-conjugated, multi-flexible end-group coumarin thiazole hybrids with outstanding bacteriostatic potential. Bioactivity screening showed that hybrid 5i, which was modified with methoxybenzene, exerted a significant inhibitory activity against MRSA (MIC=0.004mM), which was 6 times better than the anti-MRSA activity of the reference drug norfloxacin (MIC=0.025mM). Compound 5i neither conferred apparent resistance onto MRSA strains even after multiple passages nor triggered evident toxicity to human hepatocyte LO2 cells and normal mammalian cells (RAW 264.7). Molecular docking showed that highly active molecule 5i might bind to DNA gyrase by forming stable hydrogen bonds. In addition, molecular electrostatic potential surfaces were developed to explain the high antibacterial activity of the target compounds. Furthermore, preliminary mechanism studies suggested that hybrid 5i could disrupt the bacterial membrane of MRSA and insert itself into MRSA DNA to impede its replication, thus possibly becoming a potential antibacterial repressor against MRSA.

An efficient one-pot four-component Gewald reaction: Synthesis of substituted 2-aminothiophenes with coumarin–thiazole scaffolds under environmentally benign conditions

ABSTRACTAn elegant and efficient method has been outlined for the synthesis of novel 5-amino-4-[4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl]-3-arylthiophene-2-carbonitriles employing a one-pot four-component reaction of various aldehydes, 2-[4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl]acetonitrile, malononitrile and molecular sulfur independently in the presence of L-proline as a catalyst, under green reaction conditions. In an alternative approach, initially, the Knoevenagel condensation of these various aldehydes has been carried out with active methylene compounds malononitrile or 2-[4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl]acetonitrile to obtain the corresponding condensed compounds. These compounds then further subjected to a one-pot three-component Gewald reaction with molecular sulfur using sodium bicarbonate as a simple and inexpensive catalyst to obtain the target compounds. The effect of solvent and catalyst on these reactions has been screened to obtain the optimal conditions. The advantages of this protocol are the use of mild reaction conditions at ambient temperature, environmental friendliness, good yields in faster reaction times, convenient operation procedures, and broad substrate scope.

Stimuli-responsive luminescent coumarin thiazole hybrid dye: Mechanism of excited-state intramolecular double proton transfer

Recently, a novel coumarin thiazole hybrid dye with azomethine linkage is synthesized. It is revealed that the symmetrical structures 3,3'-(5,5'-((1E,1'E)-hydrazine-1,2-diylidenebis(methanylylidene))bis(2-morpholinothiazole-5,4-diyl))bis(4-hydroxy-2H-chromen-2-one) (abbreviated as CS) takes shape two intramolecular hydrogen bonds and that excited-state intramolecular proton transfer (ESIPT) takes place with thiazole nitrogen atoms [Dyes Pigments. 142, 2017, 121]. However the corresponding reaction mechanisms are lacking. This study uses density functional and time-dependent density functional theory to calculate hydrogen-bond lengths, hydrogen-bond angles, infrared vibrational spectra and Mulliken charges of relevant groups, which confirm the excited-state hydrogen-bond strengthening mechanism. Enhanced hydrogen-bond strength facilitates the ESIPT process of the CS molecule. The absorption and fluorescence emission spectra of CS in dimethyl formamide (DMF) are calculated, which are consistent with the observed results in experiment. To further illustrate mechanism of excited-state double proton transfer (ESDPT) reactions, the potential energy surfaces of CS are constructed and analyzed, which demonstrate ESDPT more likely occur stepwise rather than concertedly. The frontier molecular orbitals of CS system are also calculated and display the nature of the charge redistribution, which demonstrate that CS system exhibits light fastness because ESIPT process inhibits intramolecular charge transfer.

Viscosity induced emission of red-emitting NLOphoric coumarin morpholine-thiazole hybrid styryl dyes as FMRs: Consolidated experimental and theoretical approach

Four new coumarin hybrid styryl dyes are synthesized by condensing 4-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)-2-morpholinothiazole-5-carbaldehyde with dicyanovinylene containing active methylene intermediates and their linear and non-linear optical properties are studied. The dye having dicyanovinylene-isophorone acceptor displayed a large Stokes shift of 3702–4795 cm−1 in non-polar to polar solvent respectively. The dyes exhibit a good charge transfer characteristics and positive emission solvatochromism (∼50 nm–72 nm) in non-polar to a polar solvent which is well supported by multi-linear regression analysis. Viscosity induced enhancement study in ethanol/polyethylene glycol-400 system shows 2.71–6.78 fold increase in emission intensity. The intra and twisted-intramolecular charge transfer (ICT-TICT) characteristics were established using emission solvatochromism, polarity plots, generalised Mullikan-Hush (GMH) analysis and optimized geometry. A dye having the highest charge transfer dipole moment relatively possess the maximum two-photon absorption cross-section area (KK-1 = 165–207 GM) which was established using theoretical two-level model. The NLO properties have been investigated employing solvatochromic and computational methods and were found to be directly proportional to the polarity of the solvent. Z-scan results reveal that the dyes KK-1 and KK-2 possesses reverse saturable kind of behaviour whereas KK-3 and KK-4 show saturable kind of behaviour. From the experimental and theoretical data, these coumarin thiazole hybrid dyes can be considered as promising candidates for FMR and NLOphores.

Potential application of some coumarin derivatives incorporated thiazole ring as ecofriendly antimicrobial, flame retardant and corrosion inhibitor additives for polyurethane coating

Abstract Coumarin derivatives continue to draw the attention of synthetic organic chemists due to their versatile utility associated with them and their widely use as pharmaceuticals. Coumarin derivatives having various substituted thiazole rings at carbon-3 exhibit promising biological activities. In this research, two series of coumarin derivatives incorporated thiazole ring were prepared; coumarin thiazole derivative and benzo coumarin thiazole derivative, the structures of the products were confirmed by elemental analysis, FTIR, 1 HNMR and mass spectroscopy. The prepared coumarin derivatives I–III was incorporated physically into polyurethane coating as an additive. Experimental coatings were fabricated on a laboratory scale and applied by brush on steel and wood panels. The coated films were screened against gram-negative bacteria, gram-positive bacteria and fungi to evaluate the antimicrobial activity of the prepared coumarin derivatives. A flame retardant property, the corrosion resistance and the mechanical properties of these coated films were also examined to evaluate the drawbacks of the prepared coumarin derivatives as an additive. The obtained results showed that, the incorporation of a few amount of the prepared coumarin derivatives into polyurethane coating have led to improve the antimicrobial activity, flame retadancy, corrosion resistance, gloss and scratch hardness of the polyurethane coated films.

Aggregation induced emissive and NLOphoric coumarin thiazole hybrid dyes: Synthesis, photophysics and TD-DFT studies

Three novel coumarin thiazole hybrid dyes 2-((4-(4-hydroxy-2-oxo-2H-chromen-3-yl)-2-morpholinothiazol-5-yl)methylene)malononitrile (CSM), (E)-2-(benzo[d]thiazol-2-yl)-3-(4-(4-hydroxy-2-oxo-2H-chromen-3-yl)-2-morpholinothiazol-5-yl)acrylonitrile (CSB), (E)-2-(3-(4-(4-hydroxy-2-oxo-2H-chromen-3-yl)-2-morpholinothiazol-5-yl)-1-phenylallylidene)malononitrile (CSA) were synthesized. The newly synthesized dyes and previously reported dyes (E)-2-(3-(2-(4-(4-hydroxy-2-oxo-2H-chromen-3-yl)−2-morpholinothiazol-5-yl)vinyl)-5,5-dimethylcyclohex-2-en-1-ylidene)malononitrile (CSI) and (E)-2-(3-(2-(4-(4-methoxy-2-oxo-2H-chromen-3-yl)-2-morpholinothiazol-5-yl)vinyl)-5,5-dimethylcyclohex-2-en-1-ylidene)malononitrile (MeOCSI) were studied for their photophysical properties in selected solvents of varying polarity. CSM, CSB, CSA and CSI were studied for their aggregation studies, absolute quantum yield, lifetime studies in selected solvents. In aggregation induced emission studies, remarkable enhancement of 9 folds for CSM, 10 folds for CSB, 6 folds for CSA and 20 folds for CSI was observed at concentrations 50% of H2O in THF. All the dyes showed twisted intramolecular charge transfer (TICT) phenomenon which was evaluated using Rettig's equation. DFT and TD-DFT studies were carried out to understand their structural aspects, linear and non-linear optical properties. Experimental and computational data show good correlation with each other.

Stimuli-responsive luminescent coumarin thiazole hybrid dye: Synthesis, aggregation induced emission, thermochromism and DFT study

Novel coumarin thiazole hybrid dye with azomethine linkage was synthesized. The dye is very sparingly soluble in DMF and insoluble in other solvents. The dye shows 2 fold increase in emission enhancement on aggregation caused at 60% DMF-H2O mixture. Differential thermal analysis revealed a change from one polymorph to the other polymorph at 285 °C leading to emission in the red region. Excited State Intramolecular Proton Transfer takes place with thiazole nitrogen atom and not with N atom of azomethine linkage contrary to Pigment Yellow 101. High color value (K/S = 10.42) and light fastness (rating = 8) properties were found as compared to Pigment Yellow 101. The computed absorption and emission values were found closer to the experimental values. The pigment exhibits higher first and second order hyperpolarizabilities (24 times more α0, 248 times more β0 and 756 times more γ value than urea).

A highly selective and sensitive chemosensor derived coumarin–thiazole for colorimetric and fluorimetric detection of CN− ion in DMSO and aqueous solution: synthesis, sensing ability, Pd(II)/Pt(II) complexes and theoretical studies

A colorimetric and fluorescence turn-on cyanide probe, including coumarin–thiazole and imine (azomethine) group, has been designed and synthesized. It showed an immediate visible color change from yellow to deep red only in DMSO, and an appearance of strong yellow and green fluorescence when CN− was added to DMSO, and a mixture of DMSO:H2O (9:1), respectively. Thus, the sensor can be used to detect CN− in aqueous solution. The sensing mechanism of chemosensor 4 reactions with CN− ion was observed with the deprotonation and addition mechanisms at the same time. The mechanisms of reactions of chemosensor 4 with; CN−, F−, and AcO− were examined using 1H NMR spectroscopy, and were also theoretically supported by DFT and TD-DFT calculations. In addition, the metal complexes of chemosensor 4 with Pd(II) and Pt(II) were also synthesized and all the synthesized compounds were characterized using general spectroscopic methods (FTIR, 1H/13C NMR, and mass spectrometry), magnetic susceptibilities, and conductivity measurements. Also, the molecular structure of 4 was determined using single crystal X-ray analysis.

Resonance induced proton transfer leading to NIR emission in coumarin thiazole hybrid dyes: Synthesis and DFT insights

Two novel coumarin thiazole hybrid dyes (E)-2-(3-(2-(4-(4-hydroxy-2-oxo-2H-chromen-3-yl)-2-morpholinothiazol-5-yl)vinyl)-5,5-dimethylcyclohex-2-en-1-ylidene)malononitrile (CSI) and (E)-2-(3-(2-(4-(4-methoxy-2-oxo-2H-chromen-3-yl)-2-morpholinothiazol-5-yl)vinyl)-5,5-dimethylcyclohex-2-en-1-ylidene)malononitrile (MeOCSI) were synthesized. CSI exhibits near infrared emission with very large Stokes shift. The dye CSI shows resonance induced excited state intramolecular proton transfer (RI-ESIPT). DFT and TD-DFT calculations clearly support and define the finding.

Design, synthesis and biological evaluation of novel coumarin thiazole derivatives as α-glucosidase inhibitors

A new series of coumarin thiazole derivatives 7a-7t were synthesized, characterized by 1H NMR, 13C NMR and element analysis, evaluated for their α-glucosidase inhibitory activity. The majority of the screened compounds displayed potent inhibitory activities with IC50 values in the range of 6.24±0.07–81.69±0.39μM, when compared to the standard acarbose (IC50=43.26±0.19μM). Structure–activity relationship (SAR) studies suggest that the pattern of substitution in the phenyl ring is closely related to the biological activity of this class of compounds. Among all the tested molecules, compound 7e (IC50=6.24±0.07μM) was found to be the most active compound in the library of coumarin thiazole derivatives. Enzyme kinetic studies showed that compound 7e is a non-competitive inhibitor with a Ki of 6.86μM. Furthermore, the binding interactions of compound 7e with the active site of α-glucosidase were confirmed through molecular docking. This study has identified a new class of potent α-glucosidase inhibitors for further investigation.

Design, synthesis, characterization, antioxidant and in vitro cytotoxic activities of novel coumarin thiazole derivatives

A series of novel (Z)-3-(2-(4-(2-oxo-2H-chromen-3-yl) thiazol-2-yl-)hydrazono)indolin-2-one (8a–8d, 9) were synthesized with various substituted indole derivatives. Structures of the newly synthesized compounds were elucidated by FT-IR, 1H NMR, 13C NMR and API-ES mass spectral data. In vitro evaluation of these coumarin compounds revealed cytotoxicity from 6.2 to 18 µg/mL against CEM, 8.2 to 21 µg/mL against L1210, 09 to 19 µg/mL against molt 4/C8, 8.6 to 12 µg/mL against HL60 and 8 to 16 µg/mL against BEL7402. The antioxidant activity of the synthesized compounds was evaluated by DPPH scavenging method. Compounds 8c, 8d and 9 showed significant antioxidant activity compared with that of standard drug ascorbic acid.

Synthesis and characterization of coumarin thiazole derivative 2-(2-amino-1,3-thiazol-4-yl)-3H-benzo[f]chromen-3-one with anti-microbial activity and its potential application in antimicrobial polyurethane coating

Coumarin, thiazole and their respective derivative products are some of the oldest and most commonly known class of nitrogen and sulphur containing compounds. In recent years there has been considerable interest in this coumarin–thiazole derivatives, which have been reported to exhibit significant biological activity and are widely used as pharmaceuticals. They are capable of imparting anti-microbial activity properties when incorporated into polymers and polymer composites. In this research, coumarin–thiazole derivative 2-(2-amino-1,3-thiazol-4-yl)-3H benzo[f]chromen-3-one (compound III), was prepared and its structure was confirmed by means of its spectra data. It was also screened for its anti-microbial activity against eight different micro-organisms when physically incorporated into a polyurethane varnish formula. Experimental coatings were manufactured on a laboratory scale and applied by means of a brush on both glass and steel panels. The results of the biological activity indicated that the polyurethane varnishes containing the 2-(2-amino-1,3-thiazol-4-yl)-3H-benzo[f]chromen-3-one (compound III) derivative, exhibit a very good antimicrobial effect. The molecular modeling study revealed that it is biologically safe, it is active and it fulfills Lipinski's rule of five. The physical and mechanical resistances of the polyurethane varnish formulations were also studied to evaluate any drawbacks associated with the addition of the derivative. The studies indicate that the physical incorporation of compound III actually enhances slightly both the physical and mechanical properties.

Highly selective chemodosimeter for cyanide based on a doubly activated Michael acceptor type of coumarin thiazole fluorophore

A doubly activated Michael acceptor type of coumarin thiazole fluorophore ( 1) was prepared and applied for the detection of cyanide ions in aqueous solution. The chemodosimeter exhibited a highly selective and sensitive response to cyanide over other various anions through the Michael addition of cyanide to 1. Upon the addition of cyanide ions, the apparent color and fluorescence changes of 1 were observable with a detection limit of 2.3 μM of the cyanide anions in aqueous solution.

ChemInform Abstract: Synthesis and anti‐Helicobacter pylori Activity of 4‐(Coumarin‐3‐yl)thiazol‐2‐ylhydrazone Derivatives.

AbstractA variety of new coumarin—thiazole conjugated systems (III) (31 examples) is synthesized by Hantzsch condensation and evaluated for a selective activity against H.