New Dimethoxyaryl-Sesquiterpene Derivatives with Cytotoxic Activity Against MCF-7 Breast Cancer Cells: From Synthesis to Topoisomerase I/II Inhibition and Cell Death Mechanism Studies

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dc.catalogadorpau
dc.contributor.authorAraque, Ileana
dc.contributor.authorVergara, Rut
dc.contributor.authorMella, Jaime
dc.contributor.authorAranguiz, Pablo
dc.contributor.authorEspinoza, Luis
dc.contributor.authorSalas, Cristián O.
dc.contributor.authorFernández Barrero, Alejandro
dc.contributor.authorQuilez del Moral, José Francisco
dc.contributor.authorVillena, Joan
dc.contributor.authorCuellar, Mauricio
dc.date.accessioned2025-05-23T14:26:35Z
dc.date.available2025-05-23T14:26:35Z
dc.date.issued2025
dc.description.abstractBreast cancer is a prevalent type of cancer worldwide, leading to both high incidence and mortality, and hence, effective and safe drugs are needed. Because of this, the use of natural products and their derivatives has become a popular strategy for developing new chemotherapeutic agents. In this study, 17 new sesquiterpene-aryl derivatives were synthesized using (−)-drimenol as the starting material. The cytotoxicity of these semi-synthetic derivatives was determined in MCF-7 cells, a breast cancer model, and in a non-tumor cell line, MCF-10, to evaluate selectivity. The results show that five of these sesquiterpene derivatives had IC50 values between 9.0 and 25 µM. Of these, compound 14c stands out for its higher cytotoxicity in MCF-7 cells but lower cytotoxicity in MCF-10 cells, being more selective than daunorubicin (selective index values of 44 and 28, respectively). In addition, compound 14c induced oxidative stress in MCF-7 cells, activated caspases-3/7, and selectively inhibited topoisomerase II (TOP2) versus topoisomerase I (TOP1) in MCF-7 cells. In silico studies allowed us to propose a binding mode for 14c to the TOP2 DNA complex to validate the experimental results. Therefore, this study demonstrated the importance of aryl-sesquiterpene structures and their promising profiles in the search for new bioinspired antitumor drugs in natural products.
dc.fechaingreso.objetodigital2025-05-23
dc.format.extent24 páginas
dc.fuente.origenORCID
dc.identifier.doi10.3390/ijms26104539
dc.identifier.urihttps://www.mdpi.com/1422-0067/26/10/4539
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/104461
dc.information.autorucEscuela de Química; Salas, Cristián O.; 0000-0001-7620-2459; 101425
dc.language.isoen
dc.nota.accesocontenido completo
dc.revistaInternational Journal of Molecular Sciences
dc.rightsacceso abierto
dc.subjectaryl-sesquiterpenes
dc.subjectCytotoxic activity
dc.subjectApoptosis
dc.subjectMCF-7 cells
dc.subjectTopoisomerases I/II
dc.subjectIn silico studies
dc.subject.ddc530
dc.subject.deweyMatemática física y químicaes_ES
dc.titleNew Dimethoxyaryl-Sesquiterpene Derivatives with Cytotoxic Activity Against MCF-7 Breast Cancer Cells: From Synthesis to Topoisomerase I/II Inhibition and Cell Death Mechanism Studies
dc.typeartículo
sipa.codpersvinculados101425
sipa.trazabilidadORCID;2025-05-19
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