Cytotoxic Activity, Topoisomerase I Inhibition and In Silico Studies of New Sesquiterpene-aryl Ester Derivatives of (-) Drimenol

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dc.contributor.authorAraque, Ileana
dc.contributor.authorRamírez, Javiera
dc.contributor.authorVergara, Rut
dc.contributor.authorMella, Jaime
dc.contributor.authorAránguiz, Pablo
dc.contributor.authorEspinoza, Luis
dc.contributor.authorVera, Waleska
dc.contributor.authorMontenegro, Iván
dc.contributor.authorSalas, Cristian O.
dc.contributor.authorVillena, Joan
dc.contributor.authorCuellar, Mauricio A.
dc.date.accessioned2023-07-12T19:31:15Z
dc.date.available2023-07-12T19:31:15Z
dc.date.issued2023-05
dc.descriptionIndexación: Scopuses
dc.description.abstractIn this study, we aimed to evaluate two sets of sesquiterpene-aryl derivatives linked by an ester bond, their cytotoxic activities, and their capacity to activate caspases 3/7 and inhibit human topoisomerase I (TOP1). A total of 13 compounds were synthesized from the natural sesquiterpene (-)-drimenol and their cytotoxic activity was evaluated in vitro against three cancer cell lines: PC-3 (prostate cancer), HT-29 (colon cancer), MCF-7 (breast cancer), and an immortalized non-tumoral cell line (MCF-10). From the results, it was observed that 6a was the most promising compound due to its cytotoxic effect on three cancer cell lines and its selectivity, 6a was 100-fold more selective than 5-FU in MCF-7 and 20-fold in PC-3. It was observed that 6a also induced apoptosis by caspases 3/7 activity using a Capsase-Glo-3/7 assay kit and inhibited TOP1. A possible binding mode of 6a in a complex with TOP1-DNA was proposed by docking and molecular dynamics studies. In addition, 6a was predicted to have a good pharmacokinetic profile for oral administration. Therefore, through this study, it was demonstrated that the drimane scaffold should be considered in the search of new antitumoral agents. © 2023 by the authors.es
dc.description.urihttps://www.mdpi.com/1420-3049/28/9/3959
dc.identifier.citationMolecules Volume 28, Issue 9May 2023 Article number 3959es
dc.identifier.doi10.3390/molecules28093959
dc.identifier.issn1420-3049
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/51601
dc.language.isoenes
dc.publisherMDPIes
dc.rights.licenseAtribución 4.0 Internacional (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subjectAryl-sesquiterpene esterses
dc.subjectCaspasees
dc.subjectCytotoxic activityes
dc.subjectDockinges
dc.subjectDrimenoles
dc.subjectMolecular dynamices
dc.subjectTopoisomerase Ies
dc.titleCytotoxic Activity, Topoisomerase I Inhibition and In Silico Studies of New Sesquiterpene-aryl Ester Derivatives of (-) Drimenoles
dc.typeArtículoes
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