On the Mechanism of Action of Dragmacidins I and J, Two New Representatives of a New Class of Protein Phosphatase 1 and 2A Inhibitors

[Image: see text] Two new brominated bis(indole) alkaloids, dragmacidins I (1) and J (2), showing low micromolar cytostatic activity, along with three known congeners were isolated from the Tanzanian sponge Dragmacidon sp. and their structures determined by the analysis of their NMR and MS data. Fro...

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Autores principales: Cruz, Patricia G., Martínez Leal, Juan Fernando, Daranas, Antonio Hernández, Pérez, Marta, Cuevas, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045348/
https://www.ncbi.nlm.nih.gov/pubmed/30023878
http://dx.doi.org/10.1021/acsomega.7b01786
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author Cruz, Patricia G.
Martínez Leal, Juan Fernando
Daranas, Antonio Hernández
Pérez, Marta
Cuevas, Carmen
author_facet Cruz, Patricia G.
Martínez Leal, Juan Fernando
Daranas, Antonio Hernández
Pérez, Marta
Cuevas, Carmen
author_sort Cruz, Patricia G.
collection PubMed
description [Image: see text] Two new brominated bis(indole) alkaloids, dragmacidins I (1) and J (2), showing low micromolar cytostatic activity, along with three known congeners were isolated from the Tanzanian sponge Dragmacidon sp. and their structures determined by the analysis of their NMR and MS data. From the study of their mechanism of action, it can be concluded that the mitotic arrest at metaphase in treated tumor cells, mediated by inhibition of PP1 and/or PP2A phosphatases is involved in the observed antiproliferative activity. Differences in their bioactivities were rationalized, and a plausible binding mode is proposed on the basis of computational simulations.
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spelling pubmed-60453482018-07-16 On the Mechanism of Action of Dragmacidins I and J, Two New Representatives of a New Class of Protein Phosphatase 1 and 2A Inhibitors Cruz, Patricia G. Martínez Leal, Juan Fernando Daranas, Antonio Hernández Pérez, Marta Cuevas, Carmen ACS Omega [Image: see text] Two new brominated bis(indole) alkaloids, dragmacidins I (1) and J (2), showing low micromolar cytostatic activity, along with three known congeners were isolated from the Tanzanian sponge Dragmacidon sp. and their structures determined by the analysis of their NMR and MS data. From the study of their mechanism of action, it can be concluded that the mitotic arrest at metaphase in treated tumor cells, mediated by inhibition of PP1 and/or PP2A phosphatases is involved in the observed antiproliferative activity. Differences in their bioactivities were rationalized, and a plausible binding mode is proposed on the basis of computational simulations. American Chemical Society 2018-04-03 /pmc/articles/PMC6045348/ /pubmed/30023878 http://dx.doi.org/10.1021/acsomega.7b01786 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Cruz, Patricia G.
Martínez Leal, Juan Fernando
Daranas, Antonio Hernández
Pérez, Marta
Cuevas, Carmen
On the Mechanism of Action of Dragmacidins I and J, Two New Representatives of a New Class of Protein Phosphatase 1 and 2A Inhibitors
title On the Mechanism of Action of Dragmacidins I and J, Two New Representatives of a New Class of Protein Phosphatase 1 and 2A Inhibitors
title_full On the Mechanism of Action of Dragmacidins I and J, Two New Representatives of a New Class of Protein Phosphatase 1 and 2A Inhibitors
title_fullStr On the Mechanism of Action of Dragmacidins I and J, Two New Representatives of a New Class of Protein Phosphatase 1 and 2A Inhibitors
title_full_unstemmed On the Mechanism of Action of Dragmacidins I and J, Two New Representatives of a New Class of Protein Phosphatase 1 and 2A Inhibitors
title_short On the Mechanism of Action of Dragmacidins I and J, Two New Representatives of a New Class of Protein Phosphatase 1 and 2A Inhibitors
title_sort on the mechanism of action of dragmacidins i and j, two new representatives of a new class of protein phosphatase 1 and 2a inhibitors
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045348/
https://www.ncbi.nlm.nih.gov/pubmed/30023878
http://dx.doi.org/10.1021/acsomega.7b01786
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