Synthesis Of Coumarin Derivatives Research Articles

Rice Husk Derived Activated Carbon‐Catalyzed Synthesis of Coumarin Derivatives: Study of Anti‐Cancer Activity

Rice Husk Derived Activated Carbon‐Catalyzed Synthesis of Coumarin Derivatives: Study of Anti‐Cancer Activity

Recent Advancement in Multicomponent Synthesis of Fused Coumarin Derivatives.

The synthesis of coumarin derivatives has been an essential topic since its discovery in 1820. In bioactive compounds, the coumarin moiety serves as a backbone, as many such bioactive compounds with the coumarin moiety play a significant role in their bioactivities. Given this moiety's relevance, several researchers are developing fused-coumarin derivatives to create new drugs. Mostly the approach done for this purpose was a multicomponent reaction based. Over the years, the multicomponent reaction has gained enormous popularity, and this approach has evolved as a replacement for conventional synthetic methods. Because of all these perspectives, we have reported the various fused-coumarin derivatives synthesized using multicomponent reactions in recent years.

Synthesis of coumarin derivatives and investigation of their inhibitory effects on lung cancer cell motility

Based on the pharmaceutical potentials of coumarins, which have antitumor activity, we synthesized new coumarin derivatives and evaluated their biological activities. The new coumarin derivatives were chemically synthesized from 4-hydroxycoumarin, and their structures were confirmed by nuclear magnetic resonance data. Ten of the synthesized compounds were investigated for antimetastatic activity against lung carcinoma cells. Several of the tested compounds showed good to mild inhibitory effects on lung cancer cell motility. There were no cytotoxic effects related to the use of these compounds. 4-Hydroxycoumarin derivatives, 4h and 4i, elicited the significant inhibitory effect on lung cancer cell motility by suppressing expression of the epithelial–mesenchymal transition markers N-cadherin, Snail, and Twist.

Coumarin Hydrazide: Chemistry, Synthesis and Pharmacological Activities - A Review

Coumarins are heterocyclic compound with a benzopyrone structure. Coumarins are a large group of organic compounds found in several plants even in bacteria and fungi. The biological activities of coumarins and its derivatives includes anticoagulant, anticancer, antiulcer, antifungal, anti-HIV, antimicrobial, antiosteoporosis, antioxidant and anti- inflammatory activity. Hydrazide-hydrazone derivatives act as structural sub units in many pharmacologically active compounds including coumarins to give biological activities like antimicrobial, anticancer, antifungal, anti-inflammatory, antiviral, anti-tubercular, and antiprotozoal activity. The interest in the synthesis of coumarin derivatives has been gaining importance over the last decades, reflecting the importance of such compounds in both medical and chemical research. In this review hydrazide-hydrazone derivatives of coumarins are taken into consideration and emphasised on the anticancer, antitubercular, antimicrobial, antioxidant and antidiabetic activity of these derivatives. Keywords: Coumarin, hydrazide, heterocyclic, benzopyran, antitumor, antimicrobial, antioxidant

Design and Synthesis of Coumarin Derivatives as Cytotoxic Agents through PI3K/AKT Signaling Pathway Inhibition in HL60 and HepG2 Cancer Cells.

In this study, a series of coumarin derivatives, either alone or as hybrids with cinnamic acid, were synthesized and evaluated for their cytotoxicity against a panel of cancer cells using the MTT assay. Then, the most active compounds were inspected for their mechanism of cytotoxicity by cell-cycle analysis, RT-PCR, DNA fragmentation, and Western blotting techniques. Cytotoxic results showed that compound (4) had a significant cytotoxic effect against HL60 cells (IC50 = 8.09 µM), while compound (8b) had a noticeable activity against HepG2 cells (IC50 = 13.14 µM). Compounds (4) and (8b) mediated their cytotoxicity via PI3K/AKT pathway inhibition. These results were assured by molecular docking studies. These results support further exploratory research focusing on the therapeutic activity of coumarin derivatives as cytotoxic agents.

Synthesis of Coumarin Derivatives: A New Class of Coumarin-Based G Protein-Coupled Receptor Activators and Inhibitors.

To expand the range of daphnetin-based inhibitors/activators used for targeting G protein-coupled receptors (GPCRs) in disease treatment, twenty-five coumarin derivatives 1–25, including 7,8-dihydroxycoumarin and 7-hydroxycoumarin derivatives with various substitution patterns/groups at C3-/4- positions, were synthesized via mild Pechmann condensation and hydroxyl modification. The structures were characterized by 1H NMR, 13C NMR and ESI-MS. Their inhibition or activation activities relative to GPCRs were evaluated by double-antibody sandwich ELISA (DAS–ELISA) in vitro. The results showed that most of the coumarin derivatives possessed a moderate GPCR activation or inhibitory potency. Among them, derivatives 14, 17, 18, and 21 showed a remarkable GPCR activation potency, with EC50 values of 0.03, 0.03, 0.03, and 0.02 nM, respectively. Meanwhile, derivatives 4, 7, and 23 had significant GPCR inhibitory potencies against GPCRs with IC50 values of 0.15, 0.02, and 0.76 nM, respectively. Notably, the acylation of hydroxyl groups at the C-7 and C-8 positions of 7,8-dihydroxycoumarin skeleton or the etherification of the hydroxyl group at the C-7 position of the 7-hydroxycoumarin skeleton could successfully change GPCRs activators into inhibitors. This work demonstrated a simple and efficient approach to developing coumarin derivatives as remarkable GPCRs activators and inhibitors via molecular diversity-based synthesis.

Coumarin functionalized molecular scaffolds for the effectual detection of hazardous fluoride and cyanide.

Fluoride and cyanide contamination in drinking water imposes detrimental impacts on human health above their permissible limits. Hence, the quantitative detection of these colourless water-soluble toxins has attracted attention. Even though a plethora of chemosensors have been reported so far for the detection of fluoride and cyanide from various matrices, still their applicability is limited to a few examples. Nevertheless, recent advances in the syntheses of coumarin derivatives have shown significant impact on fluoride and cyanide detection. Therefore, this present review provides a brief overview of the application of coumarin-coupled molecular scaffolds towards the detection of perilous fluoride and cyanide along with their sensing mechanisms in order to develop more innovative, simple, sensitive, real-time responsive and cost-effective coumarin-based supramolecular chemosensors to promote next generation approaches towards the ultra-trace quantitative detection of these toxic anions.

Synthesis of coumarin derivatives in a microfluidic flow system employing the Pechmann condensation: A case study

AbstractFor the synthesis of coumarin derivatives using the Pechmann condensation scheme, an acidic ionic liquid catalyst, abbreviated as [EBsImH][HSO4], was prepared from the ring opening of 1,4‐butanesultone by 1‐ethylimidazole, followed by the addition of 1 equiv. H2SO4(c). The [EBsImH][HSO4]‐catalyzed Pechmann condensation reactions proceeded smoothly in a batch setup, with recyclable [EBsImH][HSO4] showing great catalytic activity. The acidic ionic liquid catalyst [EBsImH][HSO4] was recovered from EtOAc/H2O extraction of the product mixture, where the H2O layer was worked up and dried for reuse in consecutive runs of the Pechmann condensation reactions, maintaining >85% conversion for four times. The catalytic reactions were also carried out in a microfluidic flow setup. The flow parameters, the reactant molar amounts, and the additional H2SO4 as a modifying acid catalyst were optimized in the current case study. A minimum conversion rate of 2.8 g/hr of coumarin derivatives was demonstrated.

Cross-Coupling of Amide and Amide Derivatives to Umbelliferone Nonaflates: Synthesis of Coumarin Derivatives and Fluorescent Materials.

The Buchwald-Hartwig cross-coupling reaction between 4-methylumbelliferone-derived nonaflates with amides, carbamates, and sulfonamides is described. A wide variety of N-substituted 7-amino coumarin analogues was prepared in good to excellent yields. The photophysical properties of aqueous-soluble derivatives were determined, and they displayed auxochrome-based variations. Gram-scale synthesis provided an acrylamide analogue, which was used to fabricate a fluorescent poly(2-hydroxylethyl methacrylate) (pHEMA) hydrogel that was resistant to leaching in ultrapure H2O. We envisage that our reported protocol to access 7-amino-4-methylcoumarin derivatives will find use toward the development of new fluorescent coumarin-based probes by researchers in the field.

An Extensive Study of Coumarin Synthesis via Knoevenagel Condensation in Choline Chloride Based Deep Eutectic Solvents.

In order to preserve the environment from harmful organic solvents, a synthesis of coumarin derivatives was performed in deep eutectic solvents, which are considered as "green" due to their characteristics. Choline chloride based deep eutectic solvents (DESs) were employed, both as solvents and as catalysts, in the synthesis of coumarin derivatives via Knoevenagel condensation. In order to find the best DES for coumarin synthesis, 20 DESs were tested for the reaction of salicylaldehyde and dimethyl malonate at 80 °C. Among the twenty tested deep eutectic solvents only five were adequate for this kind of synthesis. The best DES for this reaction was found to be the one composed of choline chloride:urea (1:2). Most coumarin compounds were obtained in good to excellent yield. Compounds 1g, 2g and 2p should be pointed out due to their yields of 85, 88 and 98 %, respectively. 3-Acetylcoumarins 5a, 5c, 5d, 5e, 5f and 5g were synthesized under ultrasound irradiation and were also obtained in excellent yields of 90, 95, 98, 93, 94 and 85 %, respectively. Series of coumarin derivatives were successfully synthesized, either in choline chloide:urea DES at 80 °C or in ultrasound-assisted reaction, from different salicylaldehydes and active methylene compounds. These "green" methods were found to be very effective in Knoevenagel condensation, while DES was recycled for several cycles without any significant influence on the product yield.

Green Chemistry Approaches to the Synthesis of Coumarin Derivatives

This review is a compilation of the green synthetic methods used in the synthesis of coumarin derivatives. Coumarins are a class of compounds with a pronounced wide range of biological activities, which have found their application in medicine, pharmacology, cosmetics and food industry. Their biological activity and potential application are highly dependent on their structure. Therefore, many researchers have been performing the synthesis of coumarin derivatives on a daily basis. High demands for their synthesis often result in an increased generation of different waste chemicals. In order to minimize the utilization and generation of toxic organic substances, green synthetic methods are applied in this manner. These methods are getting more attention in the last few decades. Green chemistry methods cover a wide range of methods, including the application of ultrasound and microwaves, ionic liquids and deep eutectic solvents, solvent-free synthesis, mechanosynthesis and multicomponent reactions. All typical condensation reactions for coumarin synthesis like Knoevenagel, Perkin, Kostanecki-Robinson, Pechmann and Reformansky reactions, have been successfully performed using these green synthetic methods. According to the authors mentioned in this review, not only these methods reduce the utilization and generation of toxic chemicals, but they can also enhance the reaction performance in terms of product yields, purity, energy consumption and post-synthetic procedures when compared to the conventional methods. Due to the significance of coumarins as biologically active systems and the recent demands of reducing toxic solvents, catalysts and energy consumption, this review provides a first full literature overview on the application of green synthetic methods in the coumarin synthesis. It covers a literature search over the period from 1995-2019. The importance of this work is its comprehensive literature survey on a specific class of heterocyclic compounds, and those researchers working on the coumarin synthesis can find very useful information on the green synthetic approaches to their synthesis. There are some reviews on the coumarin synthesis, but most of them cover only specific reactions on coumarin synthesis and none of them the whole range of green chemistry methods.

Synthesis of Coumarin Derivatives as Versatile Scaffolds for GSK-3β Enzyme Inhibition.

Glycogen synthase kinase-3 (GSK-3) is involved in the phosphorylation and inactivation of glycogen synthase. GSK-3 inhibitors have been associated with a variety of diseases, including Alzheimer´s disease (AD), diabetes type II, neurologic disorders, and cancer. The inhibition of GSK-3β isoforms is likely to represent an effective strategy against AD. The present work aimed to design and synthesize coumarin derivatives to explore their potential as GSK-3β kinase inhibitors. The through different synthetic methods were used to prepare coumarin derivatives. The GSK-3β activity was measured through the ADP-Glo™ Kinase Assay, which quantifies the kinasedependent enzymatic production of ADP from ATP, using a coupled-luminescence-based reaction. A docking study was performed by using the crystallographic structure of the staurosporine/GSK-3β complex [Protein Data Bank (PDB) code: 1Q3D]. The eleven coumarin derivatives were obtained and evaluated as potential GSK-3β inhibitors. Additionally, in silico studies were performed. The results revealed that the compounds 5c, 5d, and 6b inhibited GSK-3β enzymatic activity by 38.97-49.62% at 1 mM. The other coumarin derivatives were tested at 1 mM, 1 µM, and 1 nM concentrations and were shown to be inhibitor candidates, with significant IC50 (1.224-6.875 µM) values, except for compound 7c (IC50 = 10.809 µM). Docking simulations showed polar interactions between compound 5b and Lys85 and Ser203, clarifying the mechanism of the most potent activity. The coumarin derivatives 3a and 5b, developed in this study, showed remarkable activity as GSK-3β inhibitors.

Recent Advances in the Synthesis of Coumarin Derivatives from Different Starting Materials.

The study of coumarin dates back to 1820 when coumarin was first extracted from tonka bean by Vogel. Compounds containing coumarin backbone are a very important group of compounds due to their usage in pharmacy and medicine. Properties and biological activities of coumarin derivatives have a significant role in the development of new drugs. Therefore, many different methods and techniques are developed in order to synthesize coumarin derivatives. Coumarin derivatives could be obtained from different starting materials with various methods but with big differences in yield. This review summarized various methods, techniques and reaction conditions for synthesis of coumarins from different compounds such as aldehydes, phenols, ketones and carboxylic acids.

Antioxidant activity of some N-heterocycles derived from 2-(1-(2-oxo-2H-chromen-3-yl)ethylidene) hydrazinecarbothioamide

Efficient and convenient synthesis of coumarin derivatives was accomplished via reactions of 2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)hydrazinecarbothioamide with some carbon electrophiles, e.g. maleic anhydride, dimethyl acetylenedicarboxylate, 1,2-dichloroethane, 3′-nitro-w-bromoacetophenone, N-(4-acetylphenyl)-2-chloroacetamide, ethyl cyanoacetate/3-chlorobenzaldehyde and acetylacetone to construct some N-heterocycles such as thiazolidine, thiazole, pyrimidine and pyrazolone derivatives. The structures of all synthesized products were substantiated from their analytical and spectral data. The antioxidant activities of the synthesized compounds were examined.

Synthesis of coumarin derivatives and its Ru(II) complexes encompassing pyrazole ring as a potent antidiabetic agents – A biochemical perspective

A series of two new organoruthenium complexes have been synthesized incorporated by 4-chloro-3-formyl coumarin with 4-aminoantipyrine and morpholine respectively. The ligands (CumAP and MorcumAP) were synthesized through the new route like substitution as well as condensation method. Spectral and analytical techniques such as elemental analysis, IR, UV–vis, 1H NMR and 13C NMR and XRD provided proof of the formation of the ligands and complexes. To evaluate the antidiabetic activity of synthesized ligands and their Ru(II) complexes were subjected in both in vivo and inslico approach. The results indicated that the supplementation with MorcumAP, CumAP and (CumAP)2Ru(II) complex to diabetic-induced group, activities of superoxide dismutase, catalase and glutathione peroxidase were found to be nearer to control. LPO (Lipid peroxidation) levels were analyzed in serum, liver and kidney of mice. On comparing with organic moiety ruthenium complex shows enhanced effectiveness towards anti diabetic cells. In silico studies also support the experimental results. Overall the results of revealed that the element Ru which enhance the druggability properties of the coumarin derivatives.

Recyclable cellulose nanocrystal supported Palladium nanoparticles as an efficient heterogeneous catalyst for the solvent‐free synthesis of coumarin derivatives via von Pechmann condensation

2‐Amino pyrimidine nanocellulose‐supported Palladium nanoparticles (CNC‐AMPD‐Pd) as a novel bio supported nanocatalyst was prepared and characterized by ICP‐AES, FT‐IR, XRD, SEM, TEM, TGA and EDX techniques. The nanocatalyst demonstrated outstanding performance in Pechmann condensation between different substituted phenols and ethyl acetoacetate to obtain coumarin derivatives in good to excellent yields. The catalyst is easily recycled and reused without loss of the catalytic activity. The combined merits of reusable catalyst and solvent‐free reaction conditions make the condensation with safe operation, no leaching of pd into environment, low pollution, rapid access to products and simple workup.

SYNTHESIS OF COUMARIN HETEROCYCLIC DERIVATIVES WITH IN-VITRO ANTITUBERCULER ACTIVITY

In last few decades, though significant progress has been made in the treatment and control strategies of tubercular infections by introducing new diagnostic and monitoring tools and combination therapy, it still continues to be severe problem. The need of study was only because of there are many drugs in market to treat infection but most of the drugs are showing resistance because of the same it is difficult to treat the infection. In this study we chosen coumarin nucleus for study. Thus with the aim of developing novel molecule with improved potency for treating Mycobacterium tuberculosis H37Rv strain infections and with decreased probability of developing drug resistance. The synthesis of coumarin derivatives, starting from salicyaldehyde and ethyl acetoacetate, by conventional organic reaction and results of investigations of their anti-mycobacterial activity. MICs of the synthesized compounds are compared with existing drugs Cytotoxicity. Many compounds have shown promising activity while some were inactive. It was found that Compound A1, A2, B1, B2, C1, C2 have shown promising antitubercular activity against std. Streptomycin
 Keywords: Coumarin derivative, well diffusion method, antitubercular activity.

Synthesis of coumarin derivative using polymer supported reagents

Recently, there has been a surge in use of polymer-supported reagents and catalysts become common tools for organic synthesis in what is known as polymer-assisted synthesis since they can simplify product isolation and purification. In this context, coumarin derivative 3 was prepared in good yield and high purity, starting from 3-methoxy salicylaldehyde, using reagents supported on a macroporous ion exchange resin. For this purpose, iminocoumarin and unsaturated nitrile were used as starting materials. The synthesized compounds were characterized by IR, NMR and mass spectrometry.

Synthesis of coumarin derivatives and their cytoprotective effects on t-BHP-induced oxidative damage in HepG2 cells

Coumarins are ubiquitous in higher plants and exhibit various biological actions. The aim of this study was to investigate the structure-activity relationships of coumarin derivatives on tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in human hepatoma HepG2 cells. A series of coumarin derivatives were prepared and assessed for their cytoprotective effects. Among these, a caffeoyl acid-conjugated dihydropyranocoumarin derivative, caffeoyllomatin, efficiently protected against cell damage elicited by t-BHP. Our findings suggest that caffeoyllomatin appears to be a potent cytoprotective agent.

Design and Synthesis of Coumarin Derivatives as Novel PI3K Inhibitors.

Coumarins possess a broad spectrum of biological activities and are important pharmacophores in drug developments. Since aberrant upregulation of PI3K/Akt signaling is related to uncontrolled tumor cell proliferation, enhanced migration, and adhesion-independent tumor growth, it is of interests to find novel coumarin derivatives as anticancer agents targeting the PI3K/Akt signaling pathway. A variety of coumarin derivatives possessing the pyridinylurea units were designed to increase their potency and isoform selectivity against PI3Ks. Novel coumarin analogs 4a-m were were prepared from 5-methylpyridin-2-ylamine in a straightforward way and their growth inhibitory activity against tumor cells was evaluated by a MTT assay. The inhibitory activity against PI3Kα, β, δ and γ was measured by luminescent assay. Akt phosphorylation inhibition and caspase 3 and PARP activation were measured by Western blot analysis. Apoptosis was measured by staining cells with annexin V-FITC and 7-AAD. In general, these coumarin analogs exhibited good in vitro growth inhibitory activities against tumor K562, Hela, A549 and MCF-7 cells. Some of them showed comparable or better potency than BENC-511. Compounds 4b and 4h were much more potent PI3K inhibitors than S14161 or BENC-511. In addition, 4b was more selective to PI3Kα/β over PI3Kδ/γ, while 4h was a selective PI3Kα/β/δ inhibitor. Moreover, 4h could suppress the phosphorylation of Akt and induce K562 cell apoptosis. Coumarin derivatives possessing the pyridinylurea units are potential PI3K inhibitors and anticancer agents. These findings will be helpful for the future design of more potent and selective PI3K inhibitors.