Synthesis and in vitro antitumor evaluation of honokiol derivatives

Zhu, Meilin; Li, Bohan; Ma, Hui; Huang, Xuenan; Wang, Haotian; Dai, Yiqun; Liu, Yu; Li, Hongmei; Wu, Cheng‐Zhu

doi:10.1016/j.bmcl.2019.126849

Cited by 10 publications

(6 citation statements)

References 16 publications

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“…In our previous work, we found that the benzyl group substituted with two Cl atoms at phenolic hydroxyl group of honokiol, the isomer of MAG, can significantly improve the anti-proliferative activity [ 23 ]. In this study, we found that the 2-OH or 2′-OH of MAG replaced by Cl-substituted benzyl group can also improve the anti-proliferative activity (30 μM vs. 46 μM against MCF-7).…”

Section: Resultsmentioning

confidence: 99%

“…These results indicated that free phenolic hydroxyl groups and hydrophobic side chains are the necessary active groups for magnolol to exert antitumor effects. However, in a previous study we showed that monosubstitution of a benzyl group with Cl atoms at the phenolic hydroxyl group of honokiol significantly improved the cytotoxic activity of honokiol against cancer cells [ 23 ]. In this study, we modified the phenolic hydroxyl of MAG to obtain a series of novel MAG derivatives and examined the cytotoxic activity of these derivatives against four human cancer cell lines, as well as their inhibition of the migration and invasion of MDA-MB-231 cells.…”

Section: Introductionmentioning

confidence: 99%

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Semi-Synthesis and In Vitro Anti-Cancer Evaluation of Magnolol Derivatives

et al. 2021

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Magnolol (MAG), a biphenolic neolignan, has various biological activities including antitumor effects. In this study, 15 MAG derivatives were semi-synthesized and evaluated for their in vitro anticancer activities. From these derivatives, compound 6a exhibited the best cytotoxic activity against four human cancer cell lines, with IC50 values ranging from 20.43 to 28.27 μM. Wound-healing and transwell assays showed that compound 6a significantly inhibited the migration and invasion of MDA-MB-231 cells. In addition, Western blotting experiments, performed using various concentrations of 6a, demonstrated that it downregulates the expression of HIF-1α, MMP-2, and MMP-9 in a concentration-dependent manner. Overall, these results suggest that substituting a benzyl group having F atoms substituted at the C2 position on MAG is a viable strategy for the structural optimization of MAG derivatives as anticancer agents.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Semi-Synthesis and In Vitro Anti-Cancer Evaluation of Magnolol Derivatives

et al. 2021

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“…The results showed that Compound 25 dramatically decreased the expression of HIF-1, MMP-2, and MMP-9, demonstrating that this compound inhibits the migration and invasion of I-10 cells. [30] In addition to traditional structural modifications, loading the targeting moiety triphenylphosphine onto the exposed OH of honokiol ( 26) leads to the inhibition of cell proliferation and mitochondrial complexes, stimulation of reactive oxygen species production, oxidation of mitochondrial peroxidase 3, and inhibition of mitostatin 3 phosphorylation that is more than 100 times stronger than the effect of honokiol. The antitumor activity of the compound with this targeted modification was improved by tens or even hundreds of times in vitro compared to honokiol, although the activities of disubstituted OH derivatives were inferior to the activities of the monosubstituted derivatives.…”

Section: Hydroxy Modifications Of Honokiolmentioning

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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“…1,2 Recently, they were demonstrated to have extensive and significant biological activities, 3 including antioxidative, 4 anti-angiogenesis, 5 anti-inflammatory, 6 antidepressant, 7 and antitumor properties. [8][9][10] Among these activities, the most beneficial effect of honokiol/magnolol is their suppression of the proliferation of various tumor cells. Studies reported that they exhibit anticancer properties by inhibiting proliferation, inducing differentiation and apoptosis, suppressing angiogenesis, countering metastasis, and reversing multidrug resistance.…”

Section: Introductionmentioning

confidence: 99%

“…Studies reported that they exhibit anticancer properties by inhibiting proliferation, inducing differentiation and apoptosis, suppressing angiogenesis, countering metastasis, and reversing multidrug resistance. 9,[11][12][13][14] Although honokiol/magnolol showed antitumor activities against various tumor cells, their clinical use is limited by their insolubility, low bioavailability, and vascular irritation. Moreover, oral administration of honokiol/magnolol showed weak antitumor activity in vivo.…”

Section: Introductionmentioning

confidence: 99%

Honokiol/Magnolol-Loaded Self-Assembling Lecithin-Based Mixed Polymeric Micelles (lbMPMs) for Improving Solubility to Enhance Oral Bioavailability

Lin

Cheng

Chen

et al. 2021

IJN

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Objective This study was intended to utilize lecithin-based mixed polymeric micelles ( lb MPMs) for enhancing the solubility and bioavailability of honokiol and magnolol to resolve the hindrance of their extreme hydrophobicity on the clinical applications. Methods Lecithin was selected to increase the volume of the core of lb MPMs, thereby providing a greater solubilization capacity. A series of amphiphilic polymers (sodium deoxycholate [NaDOC], Cremophor ®, and Pluronic ® series) were included with lecithin for screening and optimization. Results After preliminary evaluation and subsequentially optimization, two lb MPMs formulations composed of honokiol/magnolol:lecithin:NaDOC ( lb MPMs[NaDOC]) and honokiol/magnolol:lecithin:PP123 ( lb MPMs[PP123]) in respective ratios of 6:2:5 and 1:1:10 were optimally obtained with the mean particle sizes of 80–150 nm, encapsulation efficacy (EEs) of >90%, and drug loading (DL) of >9.0%. These lb MPMs efficiently stabilized honokiol/magnolol in phosphate-buffered saline (PBS) at room temperature or 4 °C and in fetal bovine serum or PBS at 37 °C. PK study demonstrated that lb MPMs[NaDOC] showed much improvement in enhancing bioavailability than that by lb MPMs[PP123] for both honokiol and magnolol. The absolute bioavailability for honokiol and magnolol after intravenous administration of lb MPMs[NaDOC] exhibited 0.93- and 3.4-fold increases, respectively, compared to that of free honokiol and magnolol. For oral administration with lb MPMs[NaDOC], the absolute bioavailability of honokiol was 4.8%, and the absolute and relative bioavailability of magnolol were 20.1% and 2.9-fold increase, respectively. Conclusion Overall, honokiol/magnolol loaded in lb MPMs[NaDOC] showed an improvement of solubility with suitable physical characteristics leading to enhance honokiol and magnolol bioavailability and facilitating their wider application as therapeutic agents for treating human disorders.

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Synthesis and in vitro antitumor evaluation of honokiol derivatives

Cited by 10 publications

References 16 publications

Semi-Synthesis and In Vitro Anti-Cancer Evaluation of Magnolol Derivatives

Semi-Synthesis and In Vitro Anti-Cancer Evaluation of Magnolol Derivatives

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

Honokiol/Magnolol-Loaded Self-Assembling Lecithin-Based Mixed Polymeric Micelles (lbMPMs) for Improving Solubility to Enhance Oral Bioavailability

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