Synthesis of baicalein derivatives and evaluation of their antiviral activity against arboviruses

Qian, Xijing; Zhou, He-Yang; Liu, Yan; Dong, Jia-Xiao; Tang, Wan-Da; Zhao, Ping; Tang, Hailin; Jin, Yong‐Sheng

doi:10.1016/j.bmcl.2022.128863

Cited by 5 publications

(2 citation statements)

References 21 publications

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“…Hence, a derivative obtained by the introduction of a thiocarbonyl group at the C-4 position and another prepared by setting a halophenylamino group at C-4′ showed potent antiviral activities against CHIKV, WNV ( West Nile virus ) and ZIKV, and were shown to be 5–10 times more potent than baicalein. Both derivatives showed CC 50 of 100.0 μM and EC 50 = 3.8 μM and EC 50 = 1.9 μM, respectively, in Huh7 cells [ 94 ].…”

Section: Nps With Potential Anti-zikv Activitymentioning

confidence: 99%

Natural Products and Derivatives as Potential Zika virus Inhibitors: A Comprehensive Review

Pereira

Santos

Campana

et al. 2023

Viruses

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Zika virus (ZIKV) is an arbovirus whose infection in humans can lead to severe outcomes. This article reviews studies reporting the anti-ZIKV activity of natural products (NPs) and derivatives published from 1997 to 2022, which were carried out with NPs obtained from plants (82.4%) or semisynthetic/synthetic derivatives, fungi (3.1%), bacteria (7.6%), animals (1.2%) and marine organisms (1.9%) along with miscellaneous compounds (3.8%). Classes of NPs reported to present anti-ZIKV activity include polyphenols, triterpenes, alkaloids, and steroids, among others. The highest values of the selectivity index, the ratio between cytotoxicity and antiviral activity (SI = CC50/EC50), were reported for epigallocatechin gallate (SI ≥ 25,000) and anisomycin (SI ≥ 11,900) obtained from Streptomyces bacteria, dolastane (SI = 1246) isolated from the marine seaweed Canistrocarpus cervicorni, and the flavonol myricetin (SI ≥ 862). NPs mostly act at the stages of viral adsorption and internalization in addition to presenting virucidal effect. The data demonstrate the potential of NPs for developing new anti-ZIKV agents and highlight the lack of studies addressing their molecular mechanisms of action and pre-clinical studies of efficacy and safety in animal models. To the best of our knowledge, none of the active compounds has been submitted to clinical studies.

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Section: Nps With Potential Anti-zikv Activitymentioning

confidence: 99%

Natural Products and Derivatives as Potential Zika virus Inhibitors: A Comprehensive Review

Pereira

Santos

Campana

et al. 2023

Viruses

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“…in daily diet. A variety of biological activities have been reported, including anti-inflammatory, anti-tumor, hypolipidemic, anti-fungal and viral [15]. Baicalein (BE, 5,6,7-trihydroxyflavone) is the major constituent in plants of Scutellaria baicalensis.…”

Section: Introductionmentioning

confidence: 99%

Exploration of Baicalein-Core Derivatives as Potent Antifungal Agents: SAR and Mechanism Insights

Zhou,

Yang,

et al. 2023

Molecules

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Baicalein (BE), the major component of Scutellaria Baicalensis, exhibited potently antifungal activity against drug-resistant Candida albicans, and strong inhibition on biofilm formation. Therefore, a series of baicalein-core derivatives were designed and synthesized to find more potent compounds and investigate structure–activity relationship (SAR) and mode of action (MoA). Results demonstrate that A4 and B5 exert a more potent antifungal effect (MIC80 = 0.125 μg/mL) than BE (MIC80 = 4 μg/mL) when used in combination with fluconazole (FLC), while the MIC80 of FLC dropped from 128 μg/mL to 1 μg/mL. SAR analysis indicates that the presence of 5-OH is crucial for synergistic antifungal activities, while o-dihydroxyls and vic-trihydroxyls are an essential pharmacophore, whether they are located on the A ring or the B ring of flavonoids. The MoA demonstrated that these compounds exhibited potent antifungal effects by inhibiting hypha formation of C. albicans. However, sterol composition assay and enzymatic assay conducted in vitro indicated minimal impact of these compounds on sterol biosynthesis and Eno1. These findings were further confirmed by the results of the in-silico assay, which assessed the stability of the complexes. Moreover, the inhibition of hypha of this kind of compound could be attributed to their effect on the catalytic subunit of 1,3-β-d-glucan synthase, 1,3-β-d-glucan-UDP glucosyltransferase and glycosyl-phosphatidylinositol protein, rather than inhibiting ergosterol biosynthesis and Eno1 activity by Induced-Fit Docking and Molecular Dynamics Simulations. This study presents potential antifungal agents with synergistic effects that can effectively inhibit hypha formation. It also provides new insights into the MoA.

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Design, synthesis and anti-Chikungunya virus activity of lomerizine derivatives

Chen¹,

Ying

Wang

et al. 2023

Bioorganic & Medicinal Chemistry Letters

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Synthesis of baicalein derivatives and evaluation of their antiviral activity against arboviruses

Cited by 5 publications

References 21 publications

Natural Products and Derivatives as Potential Zika virus Inhibitors: A Comprehensive Review

Natural Products and Derivatives as Potential Zika virus Inhibitors: A Comprehensive Review

Exploration of Baicalein-Core Derivatives as Potent Antifungal Agents: SAR and Mechanism Insights

Design, synthesis and anti-Chikungunya virus activity of lomerizine derivatives

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