Synthesis and biological evaluation of truncated α-tubulin-binding pironetin analogues lacking alkyl pendants in the side chain or the dihydropyrone ring
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Other documents of the author: Paños Pérez, Julián; Diaz-Oltra, Santiago; Sanchez Peris, Maria; García Pla, Jorge; Murga, Juan; Falomir, Eva; Carda, Miguel; Redondo Horcajo, Mariano; Fernando Díaz, J.; Barasoain, Isabel; Alberto Marco, J.
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Show full item recordcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/7053
comunitat-uji-handle3:10234/8639
comunitat-uji-handle4:
INVESTIGACIONMetadata
Title
Synthesis and biological evaluation of truncated α-tubulin-binding pironetin analogues lacking alkyl pendants in the side chain or the dihydropyrone ringAuthor (s)
Date
2013Publisher
Royal Society of ChemistryISSN
1477-0520; 1477-0539Type
info:eu-repo/semantics/articlePublisher version
http://pubs.rsc.org/en/content/articlepdf/2013/ob/c3ob40854jSubject
Abstract
The preparation of several new truncated analogues of the natural dihydropyrone pironetin is described. They differ from the natural product mainly in the suppression of some of the alkyl pendants in either the side ... [+]
The preparation of several new truncated analogues of the natural dihydropyrone pironetin is described. They differ from the natural product mainly in the suppression of some of the alkyl pendants in either the side chain or the dihydropyrone ring. Their cytotoxic activity and their interactions with tubulin have been investigated. It has been found that all analogues are cytotoxic towards two either sensitive or resistant tumoral cell lines with similar IC50 values in each case, thus strongly suggesting that, like natural pironetin, they also display a covalent mechanism of action. Their cytotoxicity is, however, lower than that of the parent compound. This indicates that all alkyl pendants are necessary for the full biological activity, with the ethyl group at C-4 seemingly being particularly relevant. Most likely, the alkyl groups cause a restriction in the conformational mobility of the molecule and reduce the number of available conformations. This makes it more probable that the molecule preferentially adopts a shape which fits better into the binding point in α-tubulin. [-]
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Organic & Biomolecular Chemistry, 2013, Volume 11, Issue 35Rights
This journal is © The Royal Society of Chemistry 2013
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info:eu-repo/semantics/openAccess
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