The halogenation of natural flavonoids, baicalein and chrysin, enhances their affinity to human protein kinase <scp>CK2</scp>

Marzec, Ewa; Świtalska, Marta; Winiewska-Szajewska, Maria; Wójcik, Jacek; Wietrzyk, Joanna; Maciejewska, Agnieszka; Poznański, Jarosław; Mieczkowski, Adam

doi:10.1002/iub.2298

Cited by 18 publications

(12 citation statements)

References 53 publications

(59 reference statements)

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“…Flavanones (e.g., hesperetin), flavanol (e.g., quercetin), , and flavone (e.g., baicalein) − exhibit antiviral activities. − Interestingly, a recent study has reported SARS-CoV-2 inhibition by baicalein (IC 50 0.94 ± 0.20 μM) and its cocrystallized structure with 3CL pro 10 . Apart from the 3CL pro in SARS-CoV-2, halogenated modification of the baicalein scaffold by halogen atoms bonding to carbon (C–X) of an aromatic ring could improve bioactivity. ,− Brominated baicalein (8-bromobaicalein) has shown the greatest inhibitory effect against the breast cancer cell line MCF-7 (IC 50 10 ± 3 μM) by blocking the human protein kinase CK2 . Typically, the halogen atom on the aryl halide shows an anisotropic charge distribution that can form a halogen interaction (XB).…”

Section: Introductionmentioning

confidence: 99%

Halogenated Baicalein as a Promising Antiviral Agent toward SARS-CoV-2 Main Protease

Hengphasatporn

Wilasluck

Deetanya

et al. 2022

J. Chem. Inf. Model.

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The coronavirus disease pandemic is a constant reminder that global citizens are in imminent danger of exposure to emerging infectious diseases. Therefore, developing a technique for inhibitor discovery is essential for effective drug design. Herein, we proposed fragment molecular orbital (FMO)-based virtual screening to predict the molecular binding energy of potential severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease inhibitors. The integration of quantum mechanical approaches and trajectory analysis from a microsecond molecular dynamics simulation was used to identify potential inhibitors. We identified brominated baicalein as a potent inhibitor of the SARS-CoV-2 main protease and confirmed its inhibitory activity in an in vitro assay. Brominated baicalein did not demonstrate significant toxicity in either in vitro or in vivo studies. The pair interaction energy from FMO-RIMP2/PCM and inhibitory constants based on the protease enzyme assay suggested that the brominated baicalein could be further developed into novel SARS-CoV-2 protease inhibitors.

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Section: Introductionmentioning

confidence: 99%

Halogenated Baicalein as a Promising Antiviral Agent toward SARS-CoV-2 Main Protease

Hengphasatporn

Wilasluck

Deetanya

et al. 2022

J. Chem. Inf. Model.

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“…Binding affinities of the newly synthesized compounds towards hCK2α were assessed with the low-volume differential scanning fluorimetry (nanoDSF). The shift of the temperature of thermal denaturation in the presence of 10-fold excess of a particular ligand relative to the apo form of hCK2α (ΔT m ) can be used as a semi-qualitative measure of the binding affinity [ 35 ] or inhibitory activity [ 45 ].…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Novel Halogenated Heterocycles Based on o-Phenylenediamine and Their Interactions with the Catalytic Subunit of Protein Kinase CK2

et al. 2021

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Protein kinase CK2 is a highly pleiotropic protein kinase capable of phosphorylating hundreds of protein substrates. It is involved in numerous cellular functions, including cell viability, apoptosis, cell proliferation and survival, angiogenesis, or ER-stress response. As CK2 activity is found perturbed in many pathological states, including cancers, it becomes an attractive target for the pharma. A large number of low-mass ATP-competitive inhibitors have already been developed, the majority of them halogenated. We tested the binding of six series of halogenated heterocyclic ligands derived from the commercially available 4,5-dihalo-benzene-1,2-diamines. These ligand series were selected to enable the separation of the scaffold effect from the hydrophobic interactions attributed directly to the presence of halogen atoms. In silico molecular docking was initially applied to test the capability of each ligand for binding at the ATP-binding site of CK2. HPLC-derived ligand hydrophobicity data are compared with the binding affinity assessed by low-volume differential scanning fluorimetry (nanoDSF). We identified three promising ligand scaffolds, two of which have not yet been described as CK2 inhibitors but may lead to potent CK2 kinase inhibitors. The inhibitory activity against CK2α and toxicity against four reference cell lines have been determined for eight compounds identified as the most promising in nanoDSF assay.

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“…In the most recent research, it was shown that substitution of chrysin with chlorine increases the binding affinity to human protein kinase hCK2α, which is a therapeutic target for new inhibitors used in the treatment of cancer due to the strong correlation between malignancy and abnormally high activity of this protein in cancer cells. It was observed that 8-chlorochrysin (Figure 4) had stronger binding activity to hCK2α than the reference CK2 inhibitor, 4,5,6,7-tetrabromo-1H-benzotriazole [59]. Moreover, chrysin and its porphyrin derivatives can be used in the non-invasive photodynamic therapy of human gastric cancer cells (MGC-803) and human cervical cancer cells (HeLa) [60].…”

Section: Biological Activity 41 Anticancer Activity Of Chrysin and Its Derivativesmentioning

confidence: 99%

Chrysin: Perspectives on Contemporary Status and Future Possibilities as Pro-Health Agent

2021

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Chrysin belongs to the group of natural polyphenols. It can be found, among others, in honey, propolis and fruits and has a wide range of biological activities, including the prevention of oxidative stress, inflammation, neurodegeneration and carcinogenesis. Being a part of the human diet, chrysin is considered to be a promising compound to be used in the prevention of many diseases, including cancers, diabetes and neurodegenerative diseases such as Alzheimer’s or Parkinson’s. Nevertheless, due to the low solubility of chrysin in water and under physiological conditions, its bioavailability is low. For this reason, attempts at its functionalization have been undertaken, aiming to increase its absorption and thus augment its in vivo therapeutic efficacy. The aim of this review is to summarize the most recent research on chrysin, including its sources, metabolism, pro-health effects and the effects of its functionalization on biological activity and pharmacological efficacy, evaluated both in vitro and in vivo.

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The halogenation of natural flavonoids, baicalein and chrysin, enhances their affinity to human protein kinase CK2

Cited by 18 publications

References 53 publications

Halogenated Baicalein as a Promising Antiviral Agent toward SARS-CoV-2 Main Protease

Halogenated Baicalein as a Promising Antiviral Agent toward SARS-CoV-2 Main Protease

Synthesis of Novel Halogenated Heterocycles Based on o-Phenylenediamine and Their Interactions with the Catalytic Subunit of Protein Kinase CK2

Chrysin: Perspectives on Contemporary Status and Future Possibilities as Pro-Health Agent

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