Transition metal-catalyzed synthesis of new 3-substituted coumarin derivatives as antibacterial and cytostatic agents

Aim: The aim of this study was to synthesize new coumarin-based compounds and evaluate their antibacterial and antitumor potential. Results: Using transition metal-catalyzed reactions, a series of 7-hydroxycoumarin derivatives were synthesized with aliphatic and aryl moiety attached directly at C-3 of the coumarin ring and through the ethynyl or 1,2,3-triazole linker. The 3-substituted coumarin derivative bearing bistrifluoromethylphenyl at the C-4 position of 1,2,3-triazole (33) showed strong and selective antiproliferative activity against cervical carcinoma cells. The 7-hydroxy-4-methylcoumarin with a phenyl ring directly attached to coumarin at C-3 (10) showed good potency against the methicillin-resistant Staphylococcus aureus and vancomycin-resistant strains. Conclusion: The most active coumarin derivatives owe their antiproliferative potential to the 3,5-ditrifluoromethylphenyl substituent (in 33) and antibacterial activity to the aromatic moiety (in 10); their structure can be optimized further for improved effect.

A Review on Anti-urease Potential of Coumarins

: Coumarins, a heterocyclic benzo-α-pyrones and naturally occurring ring structure that possess significant pharmacological properties, has attracted the attention of researchers and medicinal chemists to reveal the suitability of both natural and synthetic coumarins as drugs. Many compounds have been synthesized utilizing the basic coumarin structure. The diverse synthetic methods resulted in synthesis of important coumarin derivatives that offers wide range of biological properties as antimicrobial, anticancer, anti-inflammatory, antioxidant, antidiabetic and antidepressant that makes them potential drug candidate. With particular interest in ulcer coumarins have shown potential inhibition against urease enzyme. In recent years scientists have emphasized anti-urease activity of coumarins due to their low toxicity. The aim of this review is to compile data from recent research about anti-urease activities of coumarins and structure activity relationship studies of coumarin ring structure. Investigation of different structural substitution in coumarin ring may help researchers to design new compounds with strong and effective anti-urease abilities.

Synthesis and Evaluation of Antiepileptic Activity of Newly Designed Coumarin-Sulfonamide Hybrids

The combination of different heterocyclic rings to form a multifunctional compound is a new approach to get the potent and selective compounds, which can act as antiepileptic drugs. In this study we designed and synthesized the hybrid of the coumarin ring with sulfonamide moiety. Coumarin sulfonamide hybrids (CS1-CS7) were synthesized by Knoevenagel condensation of methyl anilinosulfonyl acetate with substituted salicyaldehyde in the presence of catalytic base. The synthesized hybrid compounds were characterized by means of mass, 1H & 13C NMR and FTIR spectroscopy, moreover antiepileptic activity was screened through seizure model of epilepsy using pentylenetetrazole and maximal electroshock. According to results, compound CS-2 remained to be highest potent and presented significant protection at 60 mg/kg in both the seizure models. Furthermore, compound CS-2 was also evaluated for biochemical and a histopathological study in which no significant results were obtained. In addition to former activities, compound CS-2 was also examined for liver toxicity.

Recent Developments in Coumarin Derivatives for Breast Cancer Therapy

The coumarin ring system (benzopyran-2-one, or chromen-2-one), gift in natural shown fascinating medical specialty properties, has intrigued chemists to explore the natural coumarins or artificial analogs for his or her relevance as medication. uncountable molecules supported the coumarin ring system are synthesized within the laboratories utilizing completely different artificial techniques. the variety orientating artificial routes have crystal rectifier to fascinating derivatives together with the furanocoumarins, pyranocoumarins, and coumarin sulfamates, that are found to be helpful in photochemotherapy, antitumour and anti-HIV medical care, and conjointly as stimulants for central systema nervosum, anti-inflammatory drug, anti-coagulants, medicament and dyes. In carcinoma therapy, some coumarins and their active matter 7-hydroxycoumarin derivatives have shown sulfatase and aromatase restrictive activities. Coumarin primarily based selective oestrogen receptor modulators (SERMs) and coumarin oestrogen conjugates have conjointly been expressed as an excellent potential antibreast cancer agent. carcinoma is leading reason behind death in ladies, there's a powerful focus to spot potential new drug treatments for carcinoma. Therefore, the most objective of this review is to specialise in vital coumarin analogs with antibreast cancer activities, highlight their mechanisms of action and structure-activity relationships on elect receptors in breast tissues.

Novel Inhibitors of Eukaryotic Elongation Factor 2 Kinase: In Silico, Synthesis, and in Vitro Studies

<p>Eukaryotic elongation factor 2 kinase (eEF2K) is an unusual alpha kinase whose expression is highly upregulated in various cancers and contributes to tumor growth, metastasis, and progression. More importantly, expression of eEF2K is associated with poor clinical outcome and shorter patient survival triple negative breast cancer (TNBC). Therefore, eEF2K is an emerging molecular target for development of novel targeted therapeutics and precision medicine in solid cancers. However, currently potent, and specific inhibitors of eEF2K are not available for clinical translation. In the current study, we investigated the effects of various newly designed and synthesized a series of compounds with coumarin scaffold substitutions in inhibiting eEF2K activity using <i>in silico </i>approaches and <i>in vitro </i>studies in TNBC cells. We utilized an amide substitution at 3-position on the coumarin ring with their pharmacologically active groups containing pyrrolidine, piperidine, morpholine and piperazine groups with –(CH₂)₂– bridged for aliphatic amides. To evaluate substituent effects on coumarin scaffold, boronic acid pinacol ester and boronic acids on phenyl rings were investigated using <i>in silico</i> and <i>in vitro</i> analyses. Due to their ability to form covalent binding to the target enzyme, we investigated the effects of boron containing groups on functionalized coumarin ring (3 compounds) and designed novel aliphatic and aromatic derivatives of coumarin scaffolds (10 compounds) and phenyl ring with boron groups <b>(</b>4 compounds<b>)</b>. <i>In silico</i> analysis and molecular docking studies were performed using the Glide/SP module of Maestro molecular modeling package. According to obtained results, structure activity relationship (SAR) was carried out. Among the newly designed, synthesized, and tested compounds, our <i>in vitro</i> findings revealed that several compounds displayed a highly effective eEF2K inhibition at submicromolar concentration in<i> in vitro </i>breast cancer cells. In conclusion, we identified novel eEF2K inhibitors as promising anticancer drug substance candidates which should be further evaluated by <i>in vivo</i> studies, preclinical and clinical studies.</p><br>

Novel Inhibitors of Eukaryotic Elongation Factor 2 Kinase: In Silico, Synthesis, and in Vitro Studies

<p>Eukaryotic elongation factor 2 kinase (eEF2K) is an unusual alpha kinase whose expression is highly upregulated in various cancers and contributes to tumor growth, metastasis, and progression. More importantly, expression of eEF2K is associated with poor clinical outcome and shorter patient survival triple negative breast cancer (TNBC). Therefore, eEF2K is an emerging molecular target for development of novel targeted therapeutics and precision medicine in solid cancers. However, currently potent, and specific inhibitors of eEF2K are not available for clinical translation. In the current study, we investigated the effects of various newly designed and synthesized a series of compounds with coumarin scaffold substitutions in inhibiting eEF2K activity using <i>in silico </i>approaches and <i>in vitro </i>studies in TNBC cells. We utilized an amide substitution at 3-position on the coumarin ring with their pharmacologically active groups containing pyrrolidine, piperidine, morpholine and piperazine groups with –(CH₂)₂– bridged for aliphatic amides. To evaluate substituent effects on coumarin scaffold, boronic acid pinacol ester and boronic acids on phenyl rings were investigated using <i>in silico</i> and <i>in vitro</i> analyses. Due to their ability to form covalent binding to the target enzyme, we investigated the effects of boron containing groups on functionalized coumarin ring (3 compounds) and designed novel aliphatic and aromatic derivatives of coumarin scaffolds (10 compounds) and phenyl ring with boron groups <b>(</b>4 compounds<b>)</b>. <i>In silico</i> analysis and molecular docking studies were performed using the Glide/SP module of Maestro molecular modeling package. According to obtained results, structure activity relationship (SAR) was carried out. Among the newly designed, synthesized, and tested compounds, our <i>in vitro</i> findings revealed that several compounds displayed a highly effective eEF2K inhibition at submicromolar concentration in<i> in vitro </i>breast cancer cells. In conclusion, we identified novel eEF2K inhibitors as promising anticancer drug substance candidates which should be further evaluated by <i>in vivo</i> studies, preclinical and clinical studies.</p><br>

A Review on Synthesis and Pharmacological Activity of Coumarins and Their Analogs

Background: Coumarins were reported to possess antimicrobial, antiinflammatory, antiplasmodial, antimalarial, and enzyme inhibitory properties. Furthermore, coumarins are a type of vitamin K antagonists. Coumarins had been first organized through perkin reaction; besides Knoevenagel condensation was mentioned as a critical synthetic approach for the synthesis of 3-substituted coumarins. Moreover, Pechmann, Reformatasky and Witting reactions were stated for the preparation of coumarins. Methods: We undertook a structured search of the method of preparation, the chemical reactivity and biological properties that are associated with coumarins and their analogous. Results: Coumarins display a wide range of Src Kinase and cholinesterase inhibitor activities and application of coumarins as antidiabetic, antipsychotic and antiproliferative agents has been addressed. Other properties of coumarins such as their role in antitumor, anticancer, and as antioxidants have also been reviewed. Conclusion: This review concluded that coumarin ring was mixed with other rings, a synergistic effect for each of the ring in their biological activities was obtained, such compounds were exploited to improve various important molecules which provide scaffolds for drug improvement. These compounds were used to broaden a special molecule that gives scaffolds for drug improvement.

Overview on developed synthesis procedures of coumarin heterocycles

Considering highly valuable biological and pharmaceutical properties of coumarins, the synthesis of these heterocycles has been considered for many organic and pharmaceutical chemists. This review includes the recent research in synthesis methods of coumarin systems, investigating their biological properties and describing the literature reports for the period of 2016 to the middle of 2020. In this review, we have classified the contents based on co-groups of coumarin ring. These reported methods are carried out in the classical and non-classical conditions particularly under green condition such as using green solvent, catalyst and other procedures.

6-Methyl-4-{[4-(trimethylsilyl)-1H-1,2,3-triazol-1-yl]methyl}-2H-chromen-2-one

In the title compound, C16H19N3O2Si, the dihedral angle between the coumarin ring system (r.m.s. deviation = 0.031 Å) and the triazole ring is 73.81 (8)°. In the crystal, molecules are linked into [010] chains by weak C—H...O interactions.

A derivatization-directed three-component synthesis of fluorescent spiro [dihydropyridine-4,3ʹ-indoline]s

The synthesis of spiro[chromeno[4,3- b]pyrazolo[4,3- e]pyridine-7,3ʹ-indoline]s is achieved via three-component reactions of 5-amino-3-methylpyrazole, 4-aminocoumarin, and isatin derivatives. This protocol provides expedient synthesis of 10-unsubstituted derivatives of the parent heterocyclic spiro framework and does not lead to coumarin ring opening. The synthesis is highly convergent as no by-products are present in the reaction mixtures. The spiro products show violet fluorescence emissions depending on the nature of their substituents.