Cruz PG1, Martínez Leal JF1, Daranas AH2, Pérez M1, Cuevas C1.
Author information:
1.- R&D Area, PharmaMar, S.A., Avda. de los Reyes 1, Pol. Ind. La Mina, Colmenar Viejo, Madrid 28770, Spain.
2.- Instituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas (CSIC), La Laguna, Santa Cruz de Tenerife 38206, Spain.
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.