Design and Synthesis of Pironetin Analogues with Simplified Structure and Study of Their Interactions with Microtubules

8 páginas, 4 figuras, 1 tabla, 2 esquemas -- PAGS nros. 1630-1637The preparation of a series of pironetin analogues with simplified structure is described. Their cytotoxic activity and their interactions with tubulin have been investigated. It has been found that, while less active than the parent molecule, the pironetin analogues still share the mechanism of action of the latter and compete for the same binding site to α-tubulin. Variations in the configurations of their stereocenters do not translate into relevant differences between biological activitiesFinancial support has been granted by the Spanish Ministry of Education and Science (CTQ2008-02800), by the Consellería d'Empresa, Universitat i Ciencia de la Generalitat Valenciana (ACOMP09/113) and by the BANCAJA-UJI Foundation (P1-1B2002-06 and P1-1B-2008-14). The biological work has been supported in part by grants from the Spanish Ministry of Education and Science (BIO2007-61336 and BIO2010-16351) and from the Comunidad de Madrid (BIPPED-CM) (both to J.F.D.)Peer reviewe