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

ACS Omega
Patricia G CruzCarmen Cuevas

Abstract

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.

References

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Jun 22, 2006·Mini Reviews in Medicinal Chemistry·Carmen SanmartínJuan Antonio Palop
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Citations

Feb 7, 2020·Natural Product Reports·Anthony R CarrollMichèle R Prinsep
Nov 13, 2018·Current Medicinal Chemistry·Chao Li, Dayong Shi
Jul 18, 2018·Marine Drugs·Florbela Pereira, Joao Aires-de-Sousa

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Methods Mentioned

BETA
NMR
flow cytometry
Protein Assay
Assay
fluorescence

Software Mentioned

FlowJo
Tree
Macromodel
Prism
GraphPad
jaguar p K a
Glide
Prime
Jaguar

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