Synthesis and Biological Screening of New 4-Hydroxycoumarin Derivatives and Their Palladium(II) Complexes

Avdović, Edina H.; Petrović, Isidora; Stevanović, Milena; Saso, Luciano; Marković, Jasmina M. Dimitrić; Filipović, Nenad; Živić, Miroslav; Antić, Tijana N. Cvetić; Žižić, Milan; Todorović, Nataša; Vukić, Milena; Trifunović, Srećko R.; Marković, Zoran

doi:10.1155/2021/8849568

Cited by 13 publications

(26 citation statements)

References 76 publications

(97 reference statements)

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“…Chemicals (purity > 98%) used for the synthesis were acquired from Merck, and vinegar (acetic acid 90 g/L) was purchased from the local market. Compounds 3-acetyl-4-hydroxycoumarin (1) and hydrazides (2) were prepared according to the previously reported methods [19,20]. All chemicals used in HPLC analysis were HPLC grade.…”

Section: Chemical Reagents and Instrumentsmentioning

confidence: 99%

Green One-Pot Synthesis of Coumarin-Hydroxybenzohydrazide Hybrids and Their Antioxidant Potency

et al. 2021

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Compounds from the plant world that possess antioxidant abilities are of special importance for the food and pharmaceutical industry. Coumarins are a large, widely distributed group of natural compounds, usually found in plants, often with good antioxidant capacity. The coumarin-hydroxybenzohydrazide derivatives were synthesized using a green, one-pot protocol. This procedure includes the use of an environmentally benign mixture (vinegar and ethanol) as a catalyst and solvent, as well as very easy isolation of the desired products. The obtained compounds were structurally characterized by IR and NMR spectroscopy. The purity of all compounds was determined by HPLC and by elemental microanalysis. In addition, these compounds were evaluated for their in vitro antioxidant activity. Mechanisms of antioxidative activity were theoretically investigated by the density functional theory approach and the calculated values of various thermodynamic parameters, such as bond dissociation enthalpy, proton affinity, frontier molecular orbitals, and ionization potential. In silico calculations indicated that hydrogen atom transfer and sequential proton loss–electron transfer reaction mechanisms are probable, in non-polar and polar solvents respectively. Additionally, it was found that the single-electron transfer followed by proton transfer was not an operative mechanism in either solvent. The conducted tests indicate the excellent antioxidant activity, as well as the low potential toxicity, of the investigated compounds, which makes them good candidates for potential use in food chemistry.

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Section: Chemical Reagents and Instrumentsmentioning

confidence: 99%

Green One-Pot Synthesis of Coumarin-Hydroxybenzohydrazide Hybrids and Their Antioxidant Potency

et al. 2021

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“…Based on docking results, the best bioactive compounds were used for the calculation of the ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile, which is an essential criterion for the screening of drug-like chemical compounds [49,50]. For ADMET profile estimation of selected phytochemicals, Swiss ADME [34], Data Warrior [51], and computational tools [52] were used.…”

Section: Binding Free Energy (Bfe) Estimationmentioning

confidence: 99%

Identification of α-Glucosidase Inhibitors from Scutellaria edelbergii: ESI-LC-MS and Computational Approach

et al. 2022

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The recent study investigated the in vitro anti-diabetic impact of the crude extract (MeOH) and subfractions ethyl acetate (EtOAc); chloroform; n-butanol; n-hexane; and aqueous fraction of S. edelbergii and processed the active EtOAc fraction for the identification of chemical constituents for the first time via ESI-LC-MS analysis through positive ionization mode (PIM) and negative ionization mode (NIM); the identified compounds were further validated through computational analysis via standard approaches. The crude extract and subfractions presented appreciable activity against the α-glucosidase inhibitory assay. However, the EtOAc fraction with IC50 = 0.14 ± 0.06 µg/mL revealed the maximum potential among the fractions used, followed by the MeOH and n-hexane extract with IC50 = 1.47 ± 0.14 and 2.18 ± 0.30 µg/mL, respectively. Moreover, the acarbose showed an IC50 = 377.26 ± 1.20 µg/ mL whereas the least inhibition was observed for the chloroform fraction, with an IC50 = 23.97 ± 0.14 µg/mL. Due to the significance of the EtOAc fraction, when profiled for its chemical constituents, it presented 16 compounds among which the flavonoid class was dominant, and offered eight compounds, of which six were identified in NIM, and two compounds in PIM. Moreover, five terpenoids were identified—three and two in NIM and PIM, respectively—as well as two alkaloids, both of which were detected in PIM. The EtOAc fraction also contained one phenol that was noticed in PIM. The detected flavonoids, terpenoids, alkaloids, and phenols are well-known for their diverse biomedical applications. The potent EtOAc fraction was submitted to computational analysis for further validation of α-glucosidase significance to profile the responsible compounds. The pharmacokinetic estimations and protein-ligand molecular docking results with the support of molecular dynamic simulation trajectories at 100 ns suggested that two bioactive compounds—dihydrocatalpol and leucosceptoside A—from the EtOAc fraction presented excellent drug-like properties and stable conformations; hence, these bioactive compounds could be potential inhibitors of alpha-glucosidase enzyme based on intermolecular interactions with significant residues, docking score, and binding free energy estimation. The stated findings reflect that S. edelbergii is a rich source of bioactive compounds offering potential cures for diabetes mellitus; in particular, dihydrocatalpol and leucosceptoside A could be excellent therapeutic options for the progress of novel drugs to overcome diabetes mellitus.

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“…Chemicals (purity > 98%) used for the synthesis were acquired from Merck. Compound 3-acetyl-4-hydroxycoumarin (1) was prepared according to a previously reported method [45].…”

Section: Chemical Reagents and Instrumentsmentioning

confidence: 99%

Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives

Dimić

Kaluđerović

Avdović

et al. 2022

IJMS

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In this contribution, four new compounds synthesized from 4-hydroxycoumarin and tyramine/octopamine/norepinephrine/3-methoxytyramine are characterized spectroscopically (IR and NMR), chromatographically (UHPLC-DAD), and structurally at the B3LYP/6-311++G*(d,p) level of theory. The crystal structure of the 4-hydroxycoumarin-octopamine derivative was solved and used as a starting geometry for structural optimization. Along with the previously obtained 4-hydroxycoumarin-dopamine derivative, the intramolecular interactions governing the stability of these compounds were quantified by NBO and QTAIM analyses. Condensed Fukui functions and the HOMO-LUMO gap were calculated and correlated with the number and position of OH groups in the structures. In vitro cytotoxicity experiments were performed to elucidate the possible antitumor activity of the tested substances. For this purpose, four cell lines were selected, namely human colon cancer (HCT-116), human adenocarcinoma (HeLa), human breast cancer (MDA-MB-231), and healthy human lung fibroblast (MRC-5) lines. A significant selectivity towards colorectal carcinoma cells was observed. Molecular docking and molecular dynamics studies with carbonic anhydrase, a prognostic factor in several cancers, complemented the experimental results. The calculated MD binding energies coincided well with the experimental activity, and indicated 4-hydroxycoumarin-dopamine and 4-hydroxycoumarin-3-methoxytyramine as the most active compounds. The ecotoxicology assessment proved that the obtained compounds have a low impact on the daphnia, fish, and green algae population.

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Synthesis and Biological Screening of New 4-Hydroxycoumarin Derivatives and Their Palladium(II) Complexes

Cited by 13 publications

References 76 publications

Green One-Pot Synthesis of Coumarin-Hydroxybenzohydrazide Hybrids and Their Antioxidant Potency

Green One-Pot Synthesis of Coumarin-Hydroxybenzohydrazide Hybrids and Their Antioxidant Potency

Identification of α-Glucosidase Inhibitors from Scutellaria edelbergii: ESI-LC-MS and Computational Approach

Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives

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