Novel 1,3,4-thiadiazole/oxadiazole-linked honokiol derivatives suppress cancer via inducing PI3K/Akt/mTOR-dependent autophagy

Xu, Ting; Tian, Wenyue; Zhang, Qian; Liu, Jiazheng; Liu, Zhiyan; Jin, Jing; Guo, Yong; Bai, Liping

doi:10.1016/j.bioorg.2021.105257

Cited by 16 publications

(9 citation statements)

References 43 publications

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“…Two additional targets (SARS-CoV-2 spike protein, and human ACE2 receptor) closely related to the direct infection of host cells by SARS-CoV-2 have also been included in this study, due to the reported anti-infectious ability of Scutellariae radix in other bacterial or viral diseases. A precise semi-flexible molecular docking method of CDOCKER ( Gagnon et al, 2016 ; Xu et al, 2021 ) was used to further investigate the main components of Scutellariae radix for treating COVID-19. The top 10 compounds in network pharmacology analysis and another four constituents (wogonin, oroxylin A, baicalin, and wogonoside) that were often considered to be the active ingredients of Scutellariae radix , were docked into the active centers of the aforementioned targets.…”

Section: Resultsmentioning

confidence: 99%

“…The chemical structures of compounds were extracted from PubChem, and then optimized by using “Prepare Ligands” module. Finally, each compound was docked into the protein active site by “CDOCKER” module in Discovery Studio 2021 ( Gagnon et al, 2016 ; Xu et al, 2021 ). CDOCKER is a precise semi-flexible molecular docking technology that has long been recognized by peer-reviewed journals ( Gagnon et al, 2016 ).…”

Section: Methodsmentioning

confidence: 99%

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Integrated network pharmacology analysis, molecular docking, LC-MS analysis and bioassays revealed the potential active ingredients and underlying mechanism of Scutellariae radix for COVID-19

Liu

Meng

et al. 2022

Front. Plant Sci.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Integrated network pharmacology analysis, molecular docking, LC-MS analysis and bioassays revealed the potential active ingredients and underlying mechanism of Scutellariae radix for COVID-19

Liu

Meng

et al. 2022

Front. Plant Sci.

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“…According to molecular docking results, Compound 32 could bind to the PI3K active sites. Compound 32 also prevented the migration and invasion of A549 and MDA‐MB‐231 cancer cells [34] . A series of new honokiol analogs were synthesized to develop new antiviral molecules in Scheme 13.…”

Section: Honokiol Structural Modifications and Biological Actionsmentioning

confidence: 99%

Research Progress on the Structural Modification of Magnolol and Honokiol and the Biological Activities of Their Derivatives

Guo

Feng

et al. 2023

Chemistry & Biodiversity

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Magnolol and Honokiol are the primary active components that have been identified and extracted from Magnolia officinalis, and several investigations have demonstrated that they have significant pharmacological effects. Despite their therapeutic benefits for a wide range of illnesses, research on and the implementation of these compounds have been hindered by their poor water solubility and low bioavailability. Researchers are continually using chemical methods to alter their structures to make them more effective in treating and preventing diseases. Researchers are also continuously developing derivative drugs with high efficacy and few adverse effects. This article summarizes and analyzes derivatives with significant biological activities reported in recent research obtained by structural modification. The modification sites have mainly focused on the phenolic hydroxy groups, benzene rings, and diene bonds. Changes to the allyl bisphenol structure will result in unexpected benefits, including high activity, low toxicity, and good bioavailability. Furthermore, alongside earlier experimental research in our laboratory, the structure‐activity relationships of magnolol and honokiol were preliminarily summarized, providing experimental evidence for improving their development and utilization.

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“…An ideal antiviral molecule is required to possess low cytotoxicity to host cells and high antiviral efficacy. In our previous studies [10,11], it was found that honokiol was toxic to both cancerous and non-cancer cells, probably due to the presence of two phenolic hydroxyl groups. The introduction of 1,3,4-oxadiazole-linked phenyls to honokiol (9a-9o in the literature [10]) could reduce cytotoxic effects on non-cancer cells.…”

Section: Introductionmentioning

confidence: 95%

“…In our previous studies [10,11], it was found that honokiol was toxic to both cancerous and non-cancer cells, probably due to the presence of two phenolic hydroxyl groups. The introduction of 1,3,4-oxadiazole-linked phenyls to honokiol (9a-9o in the literature [10]) could reduce cytotoxic effects on non-cancer cells. Additionally, compounds containing 1,3,4-oxadiazole moiety have recently been reported to exhibit good antiviral activity against SARS-CoV-2 [12,13].…”

Section: Introductionmentioning

confidence: 95%

Synthesis and Biological Evaluation of Honokiol Derivatives Bearing 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones as Potential Viral Entry Inhibitors against SARS-CoV-2

et al. 2021

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The 2019 coronavirus disease (COVID-19) caused by SARS-CoV-2 virus infection has posed a serious danger to global health and the economy. However, SARS-CoV-2 medications that are specific and effective are still being developed. Honokiol is a bioactive component from Magnoliae officinalis Cortex with damp-drying effect. To develop new potent antiviral molecules, a series of novel honokiol analogues were synthesized by introducing various 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones to its molecule. In a SARS-CoV-2 pseudovirus model, all honokiol derivatives were examined for their antiviral entry activities. As a result, 6a and 6p demonstrated antiviral entry effect with IC50 values of 29.23 and 9.82 µM, respectively. However, the parental honokiol had a very weak antiviral activity with an IC50 value more than 50 µM. A biolayer interfero-metry (BLI) binding assay and molecular docking study revealed that 6p binds to human ACE2 protein with higher binding affinity and lower binding energy than the parental honokiol. A competitive ELISA assay confirmed the inhibitory effect of 6p on SARS-CoV-2 spike RBD’s binding with ACE2. Importantly, 6a and 6p (TC50 > 100 μM) also had higher biological safety for host cells than honokiol (TC50 of 48.23 μM). This research may contribute to the discovery of potential viral entrance inhibitors for the SARS-CoV-2 virus, although 6p’s antiviral efficacy needs to be validated on SARS-CoV-2 viral strains in a biosafety level 3 facility.

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Novel 1,3,4-thiadiazole/oxadiazole-linked honokiol derivatives suppress cancer via inducing PI3K/Akt/mTOR-dependent autophagy

Cited by 16 publications

References 43 publications

Integrated network pharmacology analysis, molecular docking, LC-MS analysis and bioassays revealed the potential active ingredients and underlying mechanism of Scutellariae radix for COVID-19

Integrated network pharmacology analysis, molecular docking, LC-MS analysis and bioassays revealed the potential active ingredients and underlying mechanism of Scutellariae radix for COVID-19

Research Progress on the Structural Modification of Magnolol and Honokiol and the Biological Activities of Their Derivatives

Synthesis and Biological Evaluation of Honokiol Derivatives Bearing 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones as Potential Viral Entry Inhibitors against SARS-CoV-2

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