The thiophene α-terthienylmethanol isolated from Tagetes minuta inhibits angiogenesis by targeting protein kinase C isozymes α and β2

Background: Tumor angiogenesis is considered as a crucial pathologic feature of cancer with a key role in multidrug resistance (MDR). Adverse effects of the currently available drugs and the development of resistance to these remain as the hardest obstacles to defeat. Objetive: This work explores fl...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Llorens de los Ríos, María C., Lanza, Priscila A., Barbieri, Cecilia L., González, María L., Funes Chabán, Macarena, Soria, Gastón, Vera, D. Mariano A., Carpinella, María Cecilia, Joray, Mariana Belén
Formato: Artículo acceptedVersion
Lenguaje:Español
Publicado: 2022
Materias:
QD Química
Acceso en línea:http://pa.bibdigital.ucc.edu.ar/3686/1/A_LLorensdelosR%C3%ADos_Lanza_Barbieri_Gonz%C3%A1lez_FunesChab%C3%A1n_Soria_Vera_Carpinella_Joray.pdf
Aporte de:
Producción Académica Universidad Católica de Córdoba (UCCor) de Universidad Católica de Córdoba
id I38-R144-3686
record_format dspace
institution Universidad Católica de Córdoba
institution_str I-38
repository_str R-144
collection Producción Académica Universidad Católica de Córdoba (UCCor)
language Español
orig_language_str_mv spa
topic QD Química
spellingShingle QD Química
Llorens de los Ríos, María C.
Lanza, Priscila A.
Barbieri, Cecilia L.
González, María L.
Funes Chabán, Macarena
Soria, Gastón
Vera, D. Mariano A.
Carpinella, María Cecilia
Joray, Mariana Belén
The thiophene α-terthienylmethanol isolated from Tagetes minuta inhibits angiogenesis by targeting protein kinase C isozymes α and β2
topic_facet QD Química
description Background: Tumor angiogenesis is considered as a crucial pathologic feature of cancer with a key role in multidrug resistance (MDR). Adverse effects of the currently available drugs and the development of resistance to these remain as the hardest obstacles to defeat. Objetive: This work explores flora from Argentina as a source of new chemical entities with antiangiogenic activity. Methods: Tube formation assay using bovine aortic endothelial cells (BAECs) was the experiment of choice to assess antiangiogenic activity. The effect of the pure compound in cell invasiveness was investigated through the trans-well migration assay. The inhibitory effect of the pure compound on VEGFR-2 and PKC isozymes α and β2 activation was studied by molecular and massive dynamic simulations. Cytotoxicity on peripheral blood mononuclear cells and erythrocyte cells was evaluated by means of MTT and hemolysis assay, respectively. In silico prediction of pharmacological properties (ADME) and evaluation of drug-likeness features were performed using the SwissADME online tool. Results: Among the plants screened, T. minuta, showed an outstanding effect with an IC50 of 33.6 ± 3.4 μg/ml. Bio-guided isolation yielded the terthiophene α-terthienylmethanol as its active metabolite. This compound inhibited VEGF-induced tube formation with an IC50 of 2.7 ± 0.4 μM and significantly impaired the invasiveness of bovine aortic endothelial cells (BAECs) as well as of the highly aggressive breast cancer cells, MDA-MB-231, when tested at 10 μM. Direct VEGFR-2 and PKC inhibition were both explored by means of massive molecular dynamics simulations. The results obtained validated the inhibitory effect on protein kinase C (PKC) isozymes α and β2 as the main mechanism underlying its antiangiogenic activity. α-terthienylmethanol showed no evidence of toxicity against peripheral blood mononuclear and erythrocyte cells. Conclusion: These findings support this thiophene as a promising antiangiogenic phytochemical to fight against several types of cancer mainly those with MDR phenotype.
format Artículo
Artículo
acceptedVersion
author Llorens de los Ríos, María C.
Lanza, Priscila A.
Barbieri, Cecilia L.
González, María L.
Funes Chabán, Macarena
Soria, Gastón
Vera, D. Mariano A.
Carpinella, María Cecilia
Joray, Mariana Belén
author_facet Llorens de los Ríos, María C.
Lanza, Priscila A.
Barbieri, Cecilia L.
González, María L.
Funes Chabán, Macarena
Soria, Gastón
Vera, D. Mariano A.
Carpinella, María Cecilia
Joray, Mariana Belén
author_sort Llorens de los Ríos, María C.
title The thiophene α-terthienylmethanol isolated from Tagetes minuta inhibits angiogenesis by targeting protein kinase C isozymes α and β2
title_short The thiophene α-terthienylmethanol isolated from Tagetes minuta inhibits angiogenesis by targeting protein kinase C isozymes α and β2
title_full The thiophene α-terthienylmethanol isolated from Tagetes minuta inhibits angiogenesis by targeting protein kinase C isozymes α and β2
title_fullStr The thiophene α-terthienylmethanol isolated from Tagetes minuta inhibits angiogenesis by targeting protein kinase C isozymes α and β2
title_full_unstemmed The thiophene α-terthienylmethanol isolated from Tagetes minuta inhibits angiogenesis by targeting protein kinase C isozymes α and β2
title_sort thiophene α-terthienylmethanol isolated from tagetes minuta inhibits angiogenesis by targeting protein kinase c isozymes α and β2
publishDate 2022
url http://pa.bibdigital.ucc.edu.ar/3686/1/A_LLorensdelosR%C3%ADos_Lanza_Barbieri_Gonz%C3%A1lez_FunesChab%C3%A1n_Soria_Vera_Carpinella_Joray.pdf
work_keys_str_mv AT llorensdelosriosmariac thethiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT lanzapriscilaa thethiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT barbiericecilial thethiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT gonzalezmarial thethiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT funeschabanmacarena thethiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT soriagaston thethiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT veradmarianoa thethiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT carpinellamariacecilia thethiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT joraymarianabelen thethiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT llorensdelosriosmariac thiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT lanzapriscilaa thiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT barbiericecilial thiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT gonzalezmarial thiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT funeschabanmacarena thiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT soriagaston thiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT veradmarianoa thiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT carpinellamariacecilia thiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
AT joraymarianabelen thiopheneaterthienylmethanolisolatedfromtagetesminutainhibitsangiogenesisbytargetingproteinkinasecisozymesaandb2
bdutipo_str Repositorios
_version_ 1764820536272093188

Ejemplares similares