ArticleArchiv der Pharmazie2025
Insights into podophyllotoxin lactone features: New cyclolignans as potential dual tubulin-topoisomerase II inhibitors.
Article in Archiv der Pharmazie, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Nicotinonitrile based dual inhibitors of tubulin and topoisomerase II exhibit potent anticancer activity.Scientific reports · 2026Article
- Insights into podophyllotoxin lactone features: New cyclolignans as potential dual tubulin-topoisomerase II inhibitors.Archiv der Pharmazie · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Chemomodulation of natural cyclolignans as podophyllotoxin has been a successful approach to obtain semisynthetic bioactive derivates. One example of this approach is the FDA-approved drug etoposide for solid and hematological tumors. It differs from the antimitotic activity of the natural product in its mechanism of action, this drug being a topoisomerase II inhibitor instead of a tubulin antimitotic. Within the molecular requirements for the activity of these compounds, the trans-γ-lactone moiety presented in the parent compound has always been a feature to be explored to chemomodulate its bioactivity. In this study, we have obtained different compounds that comply with the molecular characteristics for antitubulin and antitopoisomerase II activity combined in a single molecule. Furthermore, we explored the influence of the trans-lactone moiety on the final activity, finding that the cis-lactone was also interesting in terms of bioactivity. The best values of cytotoxicity and cell cycle inhibition were obtained for a compound lacking the lactone ring, thus mimicking the podophyllic aldehyde functionalization, a selective antimitotic podophyllotoxin derivate. The analogs with cis-lactone also presented interesting cytotoxic activity. The present study illustrates the potential of the chemomodulation of natural products such as natural cyclolignan podophyllotoxin derivates for the discovery of new antitumor agents.
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