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11 pages, 4456 KiB

Open AccessArticle

Pharmacological Characters and Toxicity Evaluation of Coumarin Derivative LP4C as Lead Compound against Biofilm Formation of Pseudomonas aeruginosa

by Moxi Yu, Jiajia Xin, Yongsheng Liu, Yamiao Chen, Hui Zhao, Yaoyao Li, Yachen Hou, Min Jia, Bin Wang and Mingkai Li

Molecules 2023, 28(7), 3138; https://doi.org/10.3390/molecules28073138 - 31 Mar 2023

Cited by 1 | Viewed by 1040

Abstract

Pseudomonas aeruginosa-induced biofilm infection is difficult to treat and poses a significant threat to public health. Our previous study found a new coumarin derivative LP4C which exerted potent in vitro and in vivo anti-biofilm activity against Pseudomonas aeruginosa; however, the underlying [...] Read more.

Pseudomonas aeruginosa-induced biofilm infection is difficult to treat and poses a significant threat to public health. Our previous study found a new coumarin derivative LP4C which exerted potent in vitro and in vivo anti-biofilm activity against Pseudomonas aeruginosa; however, the underlying molecular mechanism and drug-likeness of LP4C is unclear. In this study, we confirmed that LP4C could inhibit the biofilm in dose-dependent manner without bactericidal activity. The transcriptomic profiling and RT-PCR result revealed that bacterial pyrimidine mediated the inhibitory activity of LP4C. The cell viability was not affected in LP4C treatment groups with the concentration under 200 μg/mL, and no death or toxicity sign was observed in mice treated by 20, 40 and 80 mg/kg LP4C during the three-week test period. Ames test presented that LP4C had no effect on the bacterial reverse mutation. In additional, pharmacokinetic results showed that LP4C was likely to have the orally bioavailable properties. Our data indicate that LP4C is a possible lead compound for the development of new anti-biofilm infection agents against Pseudomonas aeruginosa. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives II)

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17 pages, 3908 KiB

Open AccessArticle

A 7-Hydroxy 4-Methylcoumarin Enhances Melanogenesis in B16-F10 Melanoma Cells

by Taejin Kim, Kwan Bo Kim and Chang-Gu Hyun

Molecules 2023, 28(7), 3039; https://doi.org/10.3390/molecules28073039 - 29 Mar 2023

Cited by 6 | Viewed by 1977

Abstract

The objectives of this study were to investigate the melanogenetic potentials of the naturally occurring 7-hydroxy coumarin derivatives 7-hydroxy 5,6-dimethoxycoumarin (7H-5,6DM), 7-hydroxy 6,8-dimethoxycoumarin (7H-6,8DM), 7-hydroxy 6-methoxycoumarin (7H-6M), and 7-hydroxy 4-methylcoumarin (7H-4M) in the melanogenic cells model for murine B16F10 melanoma cells. The initial [...] Read more.

The objectives of this study were to investigate the melanogenetic potentials of the naturally occurring 7-hydroxy coumarin derivatives 7-hydroxy 5,6-dimethoxycoumarin (7H-5,6DM), 7-hydroxy 6,8-dimethoxycoumarin (7H-6,8DM), 7-hydroxy 6-methoxycoumarin (7H-6M), and 7-hydroxy 4-methylcoumarin (7H-4M) in the melanogenic cells model for murine B16F10 melanoma cells. The initial results indicated that melanin production and intracellular tyrosinase activity were significantly stimulated by 7H-4M but not by 7H-5,6DM, 7H-6,8DM, or 7H-6M. Therefore, our present study further investigated the melanogenic effects of 7H-4M in B16-F10 cells, as well as its mechanisms of action. In a concentration-dependent manner, 7H-4M increased intracellular tyrosinase activity, leading to the accumulation of melanin without affecting the viability of B16-F10 cells. Our study further investigated the effects of 7H-4M on melanogenesis, including its ability to promote tyrosinase activity, increase melanin content, and activate molecular signaling pathways. The results indicate that 7H-4M effectively stimulated tyrosinase activity and significantly increased the expression of melanin synthesis-associated proteins, such as microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and TRP2. Based on our findings, we can conclude that 7H-4M has the ability to activate the melanogenesis process through the upregulation of cAMP-dependent protein kinase (PKA) and the cAMP response element-binding protein (CREB). Additionally, our study showed that 7H-4M induced melanogenic effects by downregulating the extracellular signal-regulated kinase (ERK) and the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthesis kinase-3β (GSK-3β) cascades, while upregulating the JNK and p38 signaling pathways. Finally, the potential of using 7H-4M in topical applications was tested through primary human skin irritation tests. During these tests, no adverse reactions were induced by 7H-4M. In summary, our results indicate that 7H-4M regulates melanogenesis through various signaling pathways such as GSK3β/β-catenin, AKT, PKA/CREB, and MAPK. These findings suggest that 7H-4M has the potential to prevent the development of pigmentation diseases. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives II)

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15 pages, 2512 KiB

Open AccessArticle

New Azido Coumarins as Potential Agents for Fluorescent Labeling and Their “Click” Chemistry Reactions for the Conjugation with closo-Dodecaborate Anion

by Julia Laskova, Alexander Serdyukov, Irina Kosenko, Ivan Ananyev, Ekaterina Titova, Anna Druzina, Igor Sivaev, Anastasia A. Antonets, Alexey A. Nazarov and Vladimir I. Bregadze

Molecules 2022, 27(23), 8575; https://doi.org/10.3390/molecules27238575 - 05 Dec 2022

Cited by 3 | Viewed by 1541

Abstract

Novel fluorescent 7-methoxy- and 7-(diethylamino)-coumarins modified with azido-group on the side chain have been synthesized. Their photophysical properties and single crystals structure characteristics have been studied. In order to demonstrate the possibilities of fluorescent labeling, obtained coumarins have been tested with closo-dodecaborate [...] Read more.

Novel fluorescent 7-methoxy- and 7-(diethylamino)-coumarins modified with azido-group on the side chain have been synthesized. Their photophysical properties and single crystals structure characteristics have been studied. In order to demonstrate the possibilities of fluorescent labeling, obtained coumarins have been tested with closo-dodecaborate derivative bearing terminal alkynyl group. Cu^I catalyzed Huisgen 1,3-dipolar cycloaddition reaction has led to fluorescent conjugates formation. The absorption–emission spectra of the formed conjugates have been presented. The antiproliferative activity and uptake of compounds against several human cell lines were evaluated. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives II)

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34 pages, 14848 KiB

Open AccessArticle

Efficient Synthesis of Fluorescent Coumarins and Phosphorous-Containing Coumarin-Type Heterocycles via Palladium Catalyzed Cross-Coupling Reactions

by Rumen Lyapchev, Ana I. Koleva, Iskra Z. Koleva, Kristian Subev, Ivelina Madzharova, Kristina B. Simeonova, Nevena Petkova-Yankova, Bernd Morgenstern, Vesela Lozanova, Petar Y. Petrov and Rositca D. Nikolova

Molecules 2022, 27(21), 7649; https://doi.org/10.3390/molecules27217649 - 07 Nov 2022

Cited by 3 | Viewed by 1859

Abstract

Quantum-chemical calculations on the spectral properties of some aryl substituted 3-phosphonocoumarins were performed, and the effect of the substituents in the aryl moiety was evaluated. The structures possessing promising fluorescent properties were successfully synthesized via Suzuki and Sonogashira cross-coupling. The synthetic protocol was [...] Read more.

Quantum-chemical calculations on the spectral properties of some aryl substituted 3-phosphonocoumarins were performed, and the effect of the substituents in the aryl moiety was evaluated. The structures possessing promising fluorescent properties were successfully synthesized via Suzuki and Sonogashira cross-coupling. The synthetic protocol was also applied for the phosphorous chemoisomer of 3-phosphonocoumarin, 1,2-benzoxaphosphorin, and their carboxylate analogues. The optical properties of the arylated and alkynylated products were experimentally determined. The obtained quantum-chemical and experimental results give the possibility for a fine tuning of the optical properties of phosphorous-containing coumarin systems by altering the substituent at its C-6 position. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives II)

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15 pages, 4331 KiB

Open AccessArticle

Janus-Type AIE Fluorophores: Synthesis and Properties of π-Extended Coumarin-Bearing Triskelions

by Masafumi Ueda, Mirai Kokubun, Nao Yanagi, Norifumi Yamamoto and Yasuhiro Mazaki

Molecules 2022, 27(21), 7450; https://doi.org/10.3390/molecules27217450 - 02 Nov 2022

Cited by 2 | Viewed by 1749

Abstract

Janus-type triskelion-shaped fluorophores comprising coumarins bearing various electron-donating substituents (1aad, 1add, 1ccd, and 1cdd) were successfully synthesized via an intramolecular Ullmann coupling. Density functional theory (DFT) calculations indicated that all the compounds presented two different molecular surfaces, similar [...] Read more.

Janus-type triskelion-shaped fluorophores comprising coumarins bearing various electron-donating substituents (1aad, 1add, 1ccd, and 1cdd) were successfully synthesized via an intramolecular Ullmann coupling. Density functional theory (DFT) calculations indicated that all the compounds presented two different molecular surfaces, similar to Janus-type molecules. The absorption and fluorescence spectra of asymmetrical derivatives 1aad, 1add, 1ccd, and 1cdd exhibited a bathochromic shift due to their narrow highest occupied molecular orbital (HOMO) –lowest unoccupied molecular orbital (LUMO) gap. Natural transition orbital (NTO) analysis indicated that the excited state orbital overlaps differ among the C₃ symmetrical and asymmetrical dyes. These triskelion-shaped fluorophores were found to form molecular nanoaggregates in THF/H₂O mixtures and demonstrated aggregation-induced emission (AIE) enhancement characteristics as a result of restricting their molecular inversion. These results indicate that Janus-type AIE fluorophores are potentially applicable as solid-state fluorescent chiral materials, which can be optimized by controlling their molecular rearrangement in the solid state. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives II)

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17 pages, 2582 KiB

Open AccessArticle

7-Hydroxycoumarin Induces Vasorelaxation in Animals with Essential Hypertension: Focus on Potassium Channels and Intracellular Ca²⁺ Mobilization

by Rafael L. C. Jesus, Isnar L. P. Silva, Fênix A. Araújo, Raiana A. Moraes, Liliane B. Silva, Daniele S. Brito, Gabriela B. C. Lima, Quiara L. Alves and Darizy F. Silva

Molecules 2022, 27(21), 7324; https://doi.org/10.3390/molecules27217324 - 28 Oct 2022

Cited by 3 | Viewed by 1766

Abstract

Cardiovascular diseases (CVD) are the deadliest noncommunicable disease worldwide. Hypertension is the most prevalent risk factor for the development of CVD. Although there is a wide range of antihypertensive drugs, there still remains a lack of blood pressure control options for hypertensive patients. [...] Read more.

Cardiovascular diseases (CVD) are the deadliest noncommunicable disease worldwide. Hypertension is the most prevalent risk factor for the development of CVD. Although there is a wide range of antihypertensive drugs, there still remains a lack of blood pressure control options for hypertensive patients. Additionally, natural products remain crucial to the design of new drugs. The natural product 7-hydroxycoumarin (7-HC) exhibits pharmacological properties linked to antihypertensive mechanisms of action. This study aimed to evaluate the vascular effects of 7-HC in an experimental model of essential hypertension. The isometric tension measurements assessed the relaxant effect induced by 7-HC (0.001 μM–300 μM) in superior mesenteric arteries isolated from hypertensive rats (SHR, 200–300 g). Our results suggest that the relaxant effect induced by 7-HC rely on K⁺-channels (K_ATP, BK_Ca, and, to a lesser extent, K_v) activation and also on Ca²⁺ influx from sarcolemma and sarcoplasmic reticulum mobilization (inositol 1,4,5-triphosphate (IP3) and ryanodine receptors). Moreover, 7-HC diminishes the mesenteric artery’s responsiveness to α1-adrenergic agonist challenge and improves the actions of the muscarinic agonist and NO donor. The present work demonstrated that the relaxant mechanism of 7-HC in SHR involves endothelium-independent vasorelaxant factors. Additionally, 7-HC reduced vasoconstriction of the sympathetic agonist while improving vascular endothelium-dependent and independent relaxation. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives II)

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20 pages, 1266 KiB

Open AccessArticle

Challenges in the Heterologous Production of Furanocoumarins in Escherichia coli

by Joana L. Rodrigues, Daniela Gomes and Lígia R. Rodrigues

Molecules 2022, 27(21), 7230; https://doi.org/10.3390/molecules27217230 - 25 Oct 2022

Cited by 5 | Viewed by 1616

Abstract

Coumarins and furanocoumarins are plant secondary metabolites with known biological activities. As they are present in low amounts in plants, their heterologous production emerged as a more sustainable and efficient approach to plant extraction. Although coumarins biosynthesis has been positively established, furanocoumarin biosynthesis [...] Read more.

Coumarins and furanocoumarins are plant secondary metabolites with known biological activities. As they are present in low amounts in plants, their heterologous production emerged as a more sustainable and efficient approach to plant extraction. Although coumarins biosynthesis has been positively established, furanocoumarin biosynthesis has been far more challenging. This study aims to evaluate if Escherichia coli could be a suitable host for furanocoumarin biosynthesis. The biosynthetic pathway for coumarins biosynthesis in E. coli was effectively constructed, leading to the production of umbelliferone, esculetin and scopoletin (128.7, 17.6, and 15.7 µM, respectively, from tyrosine). However, it was not possible to complete the pathway with the enzymes that ultimately lead to furanocoumarins production. Prenyltransferase, psoralen synthase, and marmesin synthase did not show any activity when expressed in E. coli. Several strategies were tested to improve the enzymes solubility and activity with no success, including removing potential N-terminal transit peptides and expression of cytochrome P450 reductases, chaperones and/or enzymes to increase dimethylallylpyrophosphate availability. Considering the results herein obtained, E. coli does not seem to be an appropriate host to express these enzymes. However, new alternative microbial enzymes may be a suitable option for reconstituting the furanocoumarins pathway in E. coli. Nevertheless, until further microbial enzymes are identified, Saccharomyces cerevisiae may be considered a preferred host as it has already been proven to successfully express some of these plant enzymes. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives II)

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15 pages, 1968 KiB

Open AccessArticle

Experimental and Theoretical Study on the Homodimerization Mechanism of 3-Acetylcoumarin

by Kristina B. Simeonova, Ana I. Koleva, Anna-Mariya R. Zlatanova, Nevena I. Petkova-Yankova, Hristiyan A. Aleksandrov, Petko St. Petkov and Rositca D. Nikolova

Molecules 2022, 27(21), 7228; https://doi.org/10.3390/molecules27217228 - 25 Oct 2022

Viewed by 1039

Abstract

In the present study, the reaction conditions for homodimerization process of 3-acetylcoumarin were achieved under sonication using combination of zinc and metallic salt (ZnCl₂ or Zn(OAc)₂). Appropriate frequency and sound amplitude have been identified as significant variables for the initiation [...] Read more.

In the present study, the reaction conditions for homodimerization process of 3-acetylcoumarin were achieved under sonication using combination of zinc and metallic salt (ZnCl₂ or Zn(OAc)₂). Appropriate frequency and sound amplitude have been identified as significant variables for the initiation of the reaction. On the base of first principal calculations and experimental results, the mechanism of the reaction was investigated. The relative stability of the possible intermediates has been compared, including evaluation on the ionic and radical reaction pathways for the dimerization process. Theoretical results suggested that the radical mechanism is more favorable. The C-C bond formation between the calculated radical intermediates occurs spontaneously (∆G = −214 kJ/mol for ZnCl₂, −163 kJ/mol in the case of Zn(OAc)₂), which proves the possibility for the homodimerization of 3-acetylcoumarin via formation of radical species. Both experimental and theoretical data clarified the activation role of the solvent on the reactivity of the Zn-salt. The formation of complexes of solvent molecules with Zn-atom from the ZnCl₂ reduces the energy barrier for the dissociation of Zn-Cl bond and facilitate the formation of the dimeric product. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives II)

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38 pages, 28008 KiB

Open AccessArticle

Discovery of Novel Coumarin Derivatives as Potential Dual Inhibitors against α-Glucosidase and α-Amylase for the Management of Post-Prandial Hyperglycemia via Molecular Modelling Approaches

by Shashank M. Patil, Reshma Mary Martiz, A. M. Satish, Abdullah M. Shbeer, Mohammed Ageel, Mohammed Al-Ghorbani, Lakshmi Ranganatha V, Saravanan Parameswaran and Ramith Ramu

Molecules 2022, 27(12), 3888; https://doi.org/10.3390/molecules27123888 - 17 Jun 2022

Cited by 31 | Viewed by 2341

Abstract

Coumarin derivatives are proven for their therapeutic uses in several human diseases and disorders such as inflammation, neurodegenerative disorders, cancer, fertility, and microbial infections. Coumarin derivatives and coumarin-based scaffolds gained renewed attention for treating diabetes mellitus. The current decade witnessed the inhibiting potential [...] Read more.

Coumarin derivatives are proven for their therapeutic uses in several human diseases and disorders such as inflammation, neurodegenerative disorders, cancer, fertility, and microbial infections. Coumarin derivatives and coumarin-based scaffolds gained renewed attention for treating diabetes mellitus. The current decade witnessed the inhibiting potential of coumarin derivatives and coumarin-based scaffolds against α-glucosidase and α-amylase for the management of postprandial hyperglycemia. Hyperglycemia is a condition where an excessive amount of glucose circulates in the bloodstream. It occurs when the body lacks enough insulin or is unable to correctly utilize it. With open-source and free in silico tools, we have investigated novel 80 coumarin derivatives for their inhibitory potential against α-glucosidase and α-amylase and identified a coumarin derivative, CD-59, as a potential dual inhibitor. The ligand-based 3D pharmacophore detection and search is utilized to discover diverse coumarin-like compounds and new chemical scaffolds for the dual inhibition of α-glucosidase and α-amylase. In this regard, four novel coumarin-like compounds from the ZINC database have been discovered as the potential dual inhibitors of α-glucosidase and α-amylase (ZINC02789441 and ZINC40949448 with scaffold thiophenyl chromene carboxamide, ZINC13496808 with triazino indol thio phenylacetamide, and ZINC09781623 with chromenyl thiazole). To summarize, we propose that a coumarin derivative, CD-59, and ZINC02789441 from the ZINC database will serve as potential lead molecules with dual inhibition activity against α-glucosidase and α-amylase, thereby discovering new drugs for the effective management of postprandial hyperglycemia. From the reported scaffold, the synthesis of several novel compounds can also be performed, which can be used for drug discovery. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives II)

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14 pages, 2084 KiB

Open AccessArticle

Synthesis, Optical Characterization in Solution and Solid-State, and DFT Calculations of 3-Acetyl and 3-(1′-(2′-Phenylhydrazono)ethyl)-coumarin-(7)-substituted Derivatives

by Cesar A. Villa-Martínez, Nancy E. Magaña-Vergara, Mario Rodríguez, Juan P. Mojica-Sánchez, Ángel A. Ramos-Organillo, Joaquín Barroso-Flores, Itzia I. Padilla-Martínez and Francisco J. Martínez-Martínez

Molecules 2022, 27(12), 3677; https://doi.org/10.3390/molecules27123677 - 08 Jun 2022

Cited by 3 | Viewed by 2116

Abstract

Intramolecular charge transfer (ICT) effects are responsible for the photoluminescent properties of coumarins. Hence, optical properties with different applications can be obtained by ICT modulation. Herein, four 3-acetyl-2H-chromen-2-ones (1a–d) and their corresponding fluorescent hybrids 3- (phenylhydrazone)-chromen-2-ones ( [...] Read more.

Intramolecular charge transfer (ICT) effects are responsible for the photoluminescent properties of coumarins. Hence, optical properties with different applications can be obtained by ICT modulation. Herein, four 3-acetyl-2H-chromen-2-ones (1a–d) and their corresponding fluorescent hybrids 3- (phenylhydrazone)-chromen-2-ones (2a–d) were synthesized in 74–65% yields. The UV-Vis data were in the 295–428 nm range. The emission depends on the substituent in position C-7 bearing electron-donating groups. Compounds 1b–d showed good optical properties due to the D-π-A structural arrangement. In compounds 2a–d, there is a quenching effect of fluorescence in solution. However, in the solid, an increase is shown due to an aggregation-induced emission (AIE) effect given by the rotational restraints and stacking in the crystal. Computational calculations of the HOMO-LUMO orbitals indicate high absorbance and emission values of the molecules, and gap values represent the bathochromic effect and the electronic efficiency of the compounds. Compounds 1a–d and 2a–d are good candidates for optical applications, such as OLEDs, organic solar cells, or fluorescence markers. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives II)

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17 pages, 1994 KiB

Open AccessArticle

Effects of Coumarinyl Schiff Bases against Phytopathogenic Fungi, the Soil-Beneficial Bacteria and Entomopathogenic Nematodes: Deeper Insight into the Mechanism of Action

by Vesna Rastija, Karolina Vrandečić, Jasenka Ćosić, Gabriella Kanižai Šarić, Ivana Majić, Dejan Agić, Domagoj Šubarić, Maja Karnaš, Drago Bešlo, Mario Komar and Maja Molnar

Molecules 2022, 27(7), 2196; https://doi.org/10.3390/molecules27072196 - 28 Mar 2022

Cited by 6 | Viewed by 2597

Abstract

Coumarin derivatives have been reported as strong antifungal agents against various phytopathogenic fungi. In this study, inhibitory effects of nine coumarinyl Schiff bases were evaluated against the plant pathogenic fungi (Fusarium oxysporum f. sp. lycopersici, Fusarium culmorum, Macrophomina phaseolina and [...] Read more.

Coumarin derivatives have been reported as strong antifungal agents against various phytopathogenic fungi. In this study, inhibitory effects of nine coumarinyl Schiff bases were evaluated against the plant pathogenic fungi (Fusarium oxysporum f. sp. lycopersici, Fusarium culmorum, Macrophomina phaseolina and Sclerotinia sclerotiourum). The compounds were demonstrated to be efficient antifungal agents against Macrophomina phaseolina. The results of molecular docking on the six enzymes related to the antifungal activity suggested that the tested compounds act against plant pathogenic fungi, inhibiting plant cell-wall-degrading enzymes such as endoglucanase I and pectinase. Neither compound exhibited inhibitory effects against two beneficial bacteria (Bacillus mycoides and Bradyrhizobium japonicum) and two entomopathogenic nematodes. However, compound 9 was lethal (46.25%) for nematode Heterorhabditis bacteriophora and showed an inhibitory effect against acetylcholinesterase (AChE) (31.45%), confirming the relationship between these two activities. Calculated toxicity and the pesticide-likeness study showed that compound 9 was the least lipophilic compound with the highest aquatic toxicity. A molecular docking study showed that compounds 9 and 8 bind directly to the active site of AChE. Coumarinyl Schiff bases are promising active components of plant protection products, safe for the environment, human health, and nontarget organisms. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives II)

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17 pages, 2885 KiB

Open AccessArticle

Coumarin-Palladium(II) Complex Acts as a Potent and Non-Toxic Anticancer Agent against Pancreatic Carcinoma Cells

by Aleksandra Krstic, Aleksandar Pavic, Edina Avdovic, Zoran Markovic, Milena Stevanovic and Isidora Petrovic

Molecules 2022, 27(7), 2115; https://doi.org/10.3390/molecules27072115 - 25 Mar 2022

Cited by 5 | Viewed by 2003

Abstract

Pancreatic carcinoma still represents one of the most lethal malignant diseases in the world although some progress has been made in treating the disease in the past decades. Current multi-agent treatment options have improved the overall survival of patients, however, more effective treatment [...] Read more.

Pancreatic carcinoma still represents one of the most lethal malignant diseases in the world although some progress has been made in treating the disease in the past decades. Current multi-agent treatment options have improved the overall survival of patients, however, more effective treatment strategies are still needed. In this paper we have characterized the anticancer potential of coumarin-palladium(II) complex against pancreatic carcinoma cells. Cells viability, colony formation and migratory potential of pancreatic carcinoma cells were assessed in vitro, followed by evaluation of apoptosis induction and in vivo testing on zebrafish. Presented results showed remarkable reduction in pancreatic carcinoma cells growth both in vitro and in vivo, being effective at micromolar concentrations (0.5 μM). Treatments induced apoptosis, increased BAX/BCL-2 ratio and suppressed the expression of SOX9 and SOX18, genes shown to be significantly up-regulated in pancreatic ductal adenocarcinoma. Importantly, treatments of the zebrafish-pancreatic adenocarcinoma xenografts resulted in significant reduction in tumor mass, without provoking any adverse toxic effects including hepatotoxicity. Presented results indicate the great potential of the tested compound and the perspective of its further development towards pancreatic cancer therapy. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives II)

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11 pages, 1505 KiB

Open AccessArticle

New Red-Shifted 4-Styrylcoumarin Derivatives as Potential Fluorescent Labels for Biomolecules

by Raquel Eustáquio, João P. Prates Ramalho, Ana T. Caldeira and António Pereira

Molecules 2022, 27(5), 1461; https://doi.org/10.3390/molecules27051461 - 22 Feb 2022

Cited by 4 | Viewed by 1965

Abstract

Important scientific areas, such as cellular biology, medicine, pharmacy, and environmental sciences, are dependent on very sensitive analytical techniques to track and detect biomolecules. In this work, we develop a simple, low-cost and effective synthetic strategy to produce new red-shifted 4-styrylcoumarin derivatives as [...] Read more.

Important scientific areas, such as cellular biology, medicine, pharmacy, and environmental sciences, are dependent on very sensitive analytical techniques to track and detect biomolecules. In this work, we develop a simple, low-cost and effective synthetic strategy to produce new red-shifted 4-styrylcoumarin derivatives as promising inexpensive fluorescent labels for biomolecules. The extension of the delocalized π-electron system results in bathochromic shifts in these new coumarin derivatives, which also present large Stokes shifts. In addition, density functional theory and time-dependent density functional theory calculations helped to rationalize the photophysical properties observed by the experimental results. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives II)

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Jump to: Research

92 pages, 71810 KiB

Open AccessFeature PaperReview

An Overview on the Synthesis of Fused Pyridocoumarins with Biological Interest

by Matina D. Douka and Konstantinos E. Litinas

Molecules 2022, 27(21), 7256; https://doi.org/10.3390/molecules27217256 - 26 Oct 2022

Cited by 11 | Viewed by 2708

Abstract

Pyridocoumarins are a class of synthetic and naturally occurring organic compounds with interesting biological activities. This review focuses on the synthetic strategies for the synthesis of pyridocoumarins and presents the biological properties of those compounds. The synthesis involves the formation of the pyridine [...] Read more.

Pyridocoumarins are a class of synthetic and naturally occurring organic compounds with interesting biological activities. This review focuses on the synthetic strategies for the synthesis of pyridocoumarins and presents the biological properties of those compounds. The synthesis involves the formation of the pyridine ring, at first, from a coumarin derivative, such as aminocoumarins, hydroxycoumarins, or other coumarins. The formation of a pyranone moiety follows from an existing pyridine or piperidine or phenol derivative. For the above syntheses, [4 + 2] cycloaddition reactions, multi-component reactions (MCR), as well as metal-catalyzed reactions, are useful. Pyridocoumarins present anti-cancer, anti-HIV, antimalarial, analgesic, antidiabetic, antibacterial, antifungal, anti-inflammatory, and antioxidant activities. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives II)

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10 pages, 1918 KiB

Open AccessReview

Thiocoumarins: From the Synthesis to the Biological Applications

by Maria J. Matos, Lourdes Santana, Eugenio Uriarte and Fernanda Borges

Molecules 2022, 27(15), 4901; https://doi.org/10.3390/molecules27154901 - 31 Jul 2022

Cited by 4 | Viewed by 1730

Abstract

Coumarin is a privilege scaffold in medicinal chemistry. Coumarin derivatives are still an emerging class of highly potent pharmaceutical drugs, best known in the field of antimicrobials and anticoagulants. Thiocoumarins are a particular class of coumarins in which one or two of the [...] Read more.

Coumarin is a privilege scaffold in medicinal chemistry. Coumarin derivatives are still an emerging class of highly potent pharmaceutical drugs, best known in the field of antimicrobials and anticoagulants. Thiocoumarins are a particular class of coumarins in which one or two of the oxygen atoms are replaced by a sulfur. They are chemically subdivided in three groups: Thiocoumarins, 2-thioxocoumarins, and dithiocoumarins. This review emphasizes the rationale behind the synthesis and biological applications of the most relevant publications related to this family of compounds. Particular attention has been given to their potential as drug candidates, with particular emphasis in the last 5 years. This article is based on the most relevant information collected from multiple electronic databases, including SciFinder, Pubmed, Espacenet, and Mendeley. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives II)

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20 pages, 6905 KiB

Open AccessReview

Insight on Mercapto-Coumarins: Synthesis and Reactivity

by Eslam Reda El-Sawy, Ahmed Bakr Abdelwahab and Gilbert Kirsch

Molecules 2022, 27(7), 2150; https://doi.org/10.3390/molecules27072150 - 26 Mar 2022

Cited by 5 | Viewed by 2508

Abstract

Mercapto (or sulfanyl)-coumarins are heterocycles of great interest in the development of valuable active structures in material and biological domains. They represent a highly exploitable class of compounds that open many possibilities for further chemical transformations. The present review aims to draw focus [...] Read more.

Mercapto (or sulfanyl)-coumarins are heterocycles of great interest in the development of valuable active structures in material and biological domains. They represent a highly exploitable class of compounds that open many possibilities for further chemical transformations. The present review aims to draw focus toward the synthetic applicability of various forms of mercapto-coumarins and their representations in pharmaceuticals and industries. This work covers the literature issued from 1970 to 2021. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives II)

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