2026-09-16T09:25:45Zhttps://gredos.usal.es/oai/request
oai:gredos.usal.es:10366/1668672025-11-06T16:51:51Zcom_10366_149436com_10366_3947com_10366_3946com_10366_3823col_10366_151253
Gestión del Repositorio Documental de la Universidad de Salamanca author Hernández García, Ángela Patricia author Rosales Fernández, Celia author Miranda Vera, Carolina author Veselinova Marinova, Anzhela author García Jambrina, Pablo author García-García, Pilar author Díez Martín, David author Castro González, María Ángeles author Fuentes García, Manuel 2025-09-01T07:10:20Z 2025-09-01T07:10:20Z 2024 Hernández, Á., Rosales‐Fernández, C., Miranda‐Vera, C., Veselinova, A., Jambrina, P. G., García‐García, P., García, P. A., Díez, D., Castro, M. Á., y Fuentes, M. (2025). Insights into podophyllotoxin lactone features: New cyclolignans as potential dual tubulin‐topoisomerase II inhibitors. Archiv Der Pharmazie, 358(1), e2400600. https://doi.org/10.1002/ardp.202400600 0365-6233 http://hdl.handle.net/10366/166867 10.1002/ardp.202400600 1521-4184 [EN] 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. eng Attribution-NonCommercial-NoDerivatives 4.0 Internacional Cytotoxicity Dual-activity Molecular dynamics Natural products Podophyllic aldehyde Insights into podophyllotoxin lactone features: New cyclolignans as potential dual tubulin‐topoisomerase II inhibitors info:eu-repo/semantics/article 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 URL https://gredos.usal.es/bitstream/10366/166867/1/DCF_Hern%c3%a1ndezAP_PodophyllotoxinLactone.pdf File MD5 752dece334961b893bcddd1f9d300113 3312296 application/pdf DCF_HernándezAP_PodophyllotoxinLactone.pdf URL https://gredos.usal.es/bitstream/10366/166867/4/DCF_Hern%c3%a1ndezAP_PodophyllotoxinLactone.pdf.txt File MD5 9060dce724f951c4656565ae7f15e321 59634 text/plain DCF_HernándezAP_PodophyllotoxinLactone.pdf.txt