4.7 Review

Podophyllotoxin derivatives targeting tubulin: An update (2017-2022)

Related references

Note: Only part of the references are listed.
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Summary: This review focuses on the multidirectional pharmacological properties of Podophyllotoxin (PPT) and its derivatives (PPTs), including the crosstalk with anticancer, anti-inflammatory, immunosuppression, and antiviral effects, as well as the newly uncovered mechanisms and potential of nano delivery.

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Summary: Immunofluorescent microscopy of A549 cancer cells treated with novel alicyclic podophyllotoxin C4-esters showed 'curling' of microtubules during depolymerization. Molecular dynamics study revealed differences in curved conformations of tubulin dimer in a complex with adamantane-comprising ester and podophyllotoxin.

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Summary: A series of potential candidate molecules with excellent antitumor activity targeting tubulin and PTEN/PI3K/Akt signaling pathway were synthesized by modifying the molecule structure of podophyllotoxin (PPT) at the C-4 position. Compound 12c showed stronger antiproliferative activities against HGC-27, MCF-7, and H460 cell lines than etoposide (VP-16), with lower toxicity in healthy human cells. Further analysis revealed that 12c disrupted the dynamic equilibrium of microtubules and inhibited the process of epithelial-mesenchymal transition. The downregulation of PTEN/PI3K/Akt signaling pathway and cascade influence on the mitochondrial pathway contributed to the apoptosis of cancer cells. Therefore, 12c has the potential to be a candidate molecule for gastric cancer clinical treatment.

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Summary: This passage introduces the importance of Podophyllotoxin, a substance with potent anti-cancer and anti-viral activities, in modern drug development. It highlights the need to expand its sources and search for new production methods due to increasing market demand and insufficient natural resources.

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Novel Hybrids of Podophyllotoxin and Coumarin Inhibit the Growth and Migration of Human Oral Squamous Carcinoma Cells

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Summary: Two novel hybrids of podophyllotoxin and coumarin were synthesized and compound 12b showed potent inhibition on the proliferation of oral squamous carcinoma cell lines with low toxicity on normal cells. Mechanistic studies indicated that compound 12b induced apoptosis, cell cycle arrest, and inhibited cell migration in HSC-2 cells. Moreover, 12b disrupted microtubule network, induced autophagy, activated the AMPK pathway, and restrained the AKT/mTOR pathway, making it a promising candidate for further investigation.

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