Discovery of New 2-Phenylamino-3-acyl-1,4-naphthoquinones as Inhibitors of Cancer Cells Proliferation: Searching for Intra-Cellular Targets Playing a Role in Cancer Cells Survival

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dc.contributor.authorBenites, Julio
dc.contributor.authorValderrama, Jaime A.
dc.contributor.authorContreras, Alvaro
dc.contributor.authorEnriquez, Cinthya
dc.contributor.authorPino-Rios, Ricardo
dc.contributor.authorYanez, Osvaldo
dc.contributor.authorCalderon, Pedro Buc
dc.date.accessioned2025-01-20T20:10:28Z
dc.date.available2025-01-20T20:10:28Z
dc.date.issued2023
dc.description.abstractA series of 2-phenylamino-3-acyl-1,4-naphtoquinones were evaluated regarding their in vitro antiproliferative activities using DU-145, MCF-7 and T24 cancer cells. Such activities were discussed in terms of molecular descriptors such as half-wave potentials, hydrophobicity and molar refractivity. Compounds 4 and 11 displayed the highest antiproliferative activity against the three cancer cells and were therefore further investigated. The in silico prediction of drug likeness, using pkCSM and SwissADME explorer online, shows that compound 11 is a suitable lead molecule to be developed. Moreover, the expressions of key genes were studied in DU-145 cancer cells. They include genes involved in apoptosis (Bcl-2), tumor metabolism regulation (mTOR), redox homeostasis (GSR), cell cycle regulation (CDC25A), cell cycle progression (TP53), epigenetic (HDAC4), cell-cell communication (CCN2) and inflammatory pathways (TNF). Compound 11 displays an interesting profile because among these genes, mTOR was significantly less expressed as compared to control conditions. Molecular docking shows that compound 11 has good affinity with mTOR, unraveling a potential inhibitory effect on this protein. Due to the key role of mTOR on tumor metabolism, we suggest that impaired DU-145 cells proliferation by compound 11 is caused by a reduced mTOR expression (less mTOR protein) and inhibitory activity on mTOR protein.
dc.description.funderFondo Nacional de Ciencia y Tecnologia (FONDECYT), Chile
dc.fuente.origenWOS
dc.identifier.doi10.3390/molecules28114323
dc.identifier.eissn1420-3049
dc.identifier.urihttps://doi.org/10.3390/molecules28114323
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/92071
dc.identifier.wosidWOS:001004739400001
dc.issue.numero11
dc.language.isoen
dc.revistaMolecules
dc.rightsacceso restringido
dc.subjectcancer cells
dc.subjectquinones
dc.subjectmTOR
dc.subjectantiproliferative activity
dc.subjectmolecular descriptors
dc.subjectmolecular docking
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleDiscovery of New 2-Phenylamino-3-acyl-1,4-naphthoquinones as Inhibitors of Cancer Cells Proliferation: Searching for Intra-Cellular Targets Playing a Role in Cancer Cells Survival
dc.typeartículo
dc.volumen28
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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